Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.
A class of G-protein-coupled receptors that are specific for CANNABINOIDS such as those derived from CANNABIS. They also bind a structurally distinct class of endogenous factors referred to as ENDOCANNABINOIDS. The receptor class may play a role in modulating the release of signaling molecules such as NEUROTRANSMITTERS and CYTOKINES.
Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.
A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.
A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.
OXAZINES with a fused BENZENE ring.
Monohydroxy derivatives of cyclohexanes that contain the general formula R-C6H11O. They have a camphorlike odor and are used in making soaps, insecticides, germicides, dry cleaning, and plasticizers.
Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.
A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.
Compounds that interact with and modulate the activity of CANNABINOID RECEPTORS.
Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.
Morpholines are organic compounds containing a morpholine ring, which is a saturated six-membered heterocycle made up of four carbon atoms and two oxygen atoms (OCC1CCO), often used as functional groups in pharmaceuticals, agrochemicals, and materials science due to their versatile chemical properties.
Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.
Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
Amides composed of unsaturated aliphatic FATTY ACIDS linked with AMINES by an amide bond. They are most prominent in ASTERACEAE; PIPERACEAE; and RUTACEAE; and also found in ARISTOLOCHIACEAE; BRASSICACEAE; CONVOLVULACEAE; EUPHORBIACEAE; MENISPERMACEAE; POACEAE; and SOLANACEAE. They are recognized by their pungent taste and for causing numbing and salivation.
A family of hexahydropyridines.
Bornanes are a class of bicyclic organic compounds, specifically sesquiterpenes, that contain a bornane skeleton, consisting of a cyclohexane ring fused to a cyclopentane ring, and can be found in various essential oils and plants.
Arachidonic acids are polyunsaturated fatty acids, specifically a type of omega-6 fatty acid, that are essential for human nutrition and play crucial roles in various biological processes, including inflammation, immunity, and cell signaling. They serve as precursors to eicosanoids, which are hormone-like substances that mediate a wide range of physiological responses.
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
GLYCEROL esterified with FATTY ACIDS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Amidohydrolases are enzymes that catalyze the hydrolysis of amides and related compounds, playing a crucial role in various biological processes including the breakdown and synthesis of bioactive molecules.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Compound isolated from Cannabis sativa extract.
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
An enzyme that catalyzes the hydrolysis of glycerol monoesters of long-chain fatty acids EC 3.1.1.23.
The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.
Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.
Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Drugs that bind to and activate dopamine receptors.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A physiologically inactive constituent of Cannabis sativa L.
The plant genus in the Cannabaceae plant family, Urticales order, Hamamelidae subclass. The flowering tops are called many slang terms including pot, marijuana, hashish, bhang, and ganja. The stem is an important source of hemp fiber.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT2 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT2 receptor subtypes.
Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.
Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).
A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.
Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.
The observable response an animal makes to any situation.
Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.
Phenomena and pharmaceutics of compounds that bind to the same receptor binding-site as an agonist (DRUG AGONISM) for that receptor but exerts the opposite pharmacological effect.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.
Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.
Derivatives of carbamic acid, H2NC(=O)OH. Included under this heading are N-substituted and O-substituted carbamic acids. In general carbamate esters are referred to as urethanes, and polymers that include repeating units of carbamate are referred to as POLYURETHANES. Note however that polyurethanes are derived from the polymerization of ISOCYANATES and the singular term URETHANE refers to the ethyl ester of carbamic acid.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.
A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.
Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Compounds based on benzene fused to oxole. They can be formed from methylated CATECHOLS such as EUGENOL.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.
An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.
Resorcinols are aromatic organic compounds containing two hydroxyl groups attached to a benzene ring, known for their antiseptic and antibacterial properties, used in various medical and cosmetic applications.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.
Drugs that bind to and activate excitatory amino acid receptors.
The most common inhibitory neurotransmitter in the central nervous system.
Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.
Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise.
Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.
Inbred ICR mice are a strain of albino laboratory mice that have been selectively bred for consistent genetic makeup and high reproductive performance, making them widely used in biomedical research for studies involving reproduction, toxicology, pharmacology, and carcinogenesis.
The physical activity of a human or an animal as a behavioral phenomenon.
Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.
Six-carbon alicyclic hydrocarbons.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.

Cannabinoid receptor activation in the rostral ventrolateral medulla oblongata evokes cardiorespiratory effects in anaesthetised rats. (1/177)

1. The nature of the cardiorespiratory effects mediated by cannabinoids in the hindbrain is poorly understood. In the present study we investigated whether cannabinoid receptor activation in the rostral ventrolateral medulla oblongata (RVLM) affects cardiovascular and/or respiratory function. 2. Initially, we looked for evidence of CB1 receptor gene expression in rostral and caudal sections of the rat ventrolateral medulla (VLM) using reverse transcription-polymerase chain reaction. Second, the potent cannabinoid receptor agonists WIN55,212-2 (0.05, 0.5 or 5 pmol per 50 nl) and HU-210 (0.5 pmol per 50 nl) or the CB1 receptor antagonist/inverse agonist AM281 (1 pmol per 100 nl) were microinjected into the RVLM of urethane-anaesthetised, immobilised and mechanically ventilated male Sprague-Dawley rats (n=22). Changes in splanchnic nerve activity (sSNA), phrenic nerve activity (PNA), mean arterial pressure (MAP) and heart rate (HR) in response to cannabinoid administration were recorded. 3. The CB1 receptor gene was expressed throughout the VLM. Unilateral microinjection of WIN55,212-2 into the RVLM evoked short-latency, dose-dependent increases in sSNA (0.5 pmol; 175+/-8%, n=5) and MAP (0.5 pmol; 26+/-3%, n=8) and abolished PNA (0.5 pmol; duration of apnoea: 5.4+/-0.4 s, n=8), with little change in HR (P<0.005). HU-210, structurally related to Delta9-tetrahydrocannabinol (THC), evoked similar effects when microinjected into the RVLM (n=4). Surprisingly, prior microinjection of AM281 produced agonist-like effects, as well as significantly attenuated the response to subsequent injection of WIN55,212-2 (0.5 pmol, n=4). 4. The present study reveals CB1 receptor gene expression in the rat VLM and demonstrates sympathoexcitation, hypertension and respiratory inhibition in response to RVLM-administered cannabinoids. These findings suggest a novel link between CB1 receptors in this region of the hindbrain and the central cardiorespiratory effects of cannabinoids. The extent to which these central effects contribute to the cardiovascular and respiratory outcomes of cannabis use remains to be investigated.  (+info)

Involvement of cannabinoid receptors in gut motility and visceral perception. (2/177)

From a historical perspective to the present day, all the evidence suggests that activation of cannabinoid receptors (CBRs) is beneficial for gut discomfort and pain, which are symptoms related to dysmotility and visceral perception. CBRs comprise G-protein coupled receptors that are predominantly in enteric and central neurones (CB1R) and immune cells (CB2R). In the last decade, evidence obtained from the use of selective agonists and inverse agonists/antagonists indicates that manipulation of CB1R can alter (1) sensory processing from the gut, (2) brain integration of brain-gut axis, (3) extrinsic control of the gut and (4) intrinsic control by the enteric nervous system. The extent to which activation of CB1R is most critical at these different levels is related to the region of the GI tract. The upper GI tract is strongly influenced by CB1R activation on central vagal pathways, whereas intestinal peristalsis can be modified by CB1R activation in the absence of extrinsic input. Actions at multiple levels make the CB1R a target for the treatment of functional bowel disorders, such as IBS. Since low-grade inflammation may act as a trigger for occurrence of IBS, CB2R modulation could be beneficial, but there is little supporting evidence for this yet. The challenge is to accomplish CBR activation while minimizing adverse effects and abuse liabilities. Potential therapeutic strategies involve increasing signaling by endocannabinoids (EC). The pathways involved in the biosynthesis, uptake and degradation of EC provide opportunities for modulation of CB1R and some recent evidence with inhibitors of EC uptake and metabolism suggest that these could be exploited for therapeutic gain.  (+info)

Cannabinoid receptor-independent actions of the aminoalkylindole WIN 55,212-2 on trigeminal sensory neurons. (3/177)

The prototypical aminoalkylindole cannabinoid WIN 55,212-2 (WIN-2) has been shown to produce antihyperalgesia through a peripheral mechanism of action. However, it is not known whether WIN-2 exerts this action directly via cannabinoid receptors located on primary afferents or if other, perhaps indirect or noncannabinoid, mechanisms are involved. To address this question, we have examined the specific actions of WIN-2 on trigeminal ganglion (TG) neurons in vitro by quantifying its ability to modulate the evoked secretion of the proinflammatory neuropeptide CGRP as well as the inflammatory mediator-induced generation of cAMP. WIN-2 evoked CGRP release from TG neurons in vitro (EC(50)=26 microm) in a concentration- and calcium-dependent manner, which was mimicked by the cannabinoid receptor-inactive enantiomer WIN 55,212-3 (WIN-3). Moreover, WIN-2-evoked CGRP release was attenuated by the nonselective cation channel blocker ruthenium red but not by the vanilloid receptor type 1 (TRPV1) antagonist capsazepine, suggesting that, unlike certain endogenous and synthetic cannabinoids, WIN-2 is not a TRPV1 agonist but rather acts at an as yet unidentified cation channel. The inhibitory effects of WIN-2 on TG neurons were also examined. WIN-2 neither inhibited capsaicin-evoked CGRP release nor did it inhibit forskolin-, isoproteranol- or prostaglandin E(2)-stimulated cAMP accumulation. On the other hand, WIN-2 significantly inhibited (EC(50)=1.7 microm) 50 mm K(+)-evoked CGRP release by approximately 70%. WIN-2 inhibition of 50 mm K(+)-evoked CGRP release was not reversed by antagonists of cannabinoid type 1 (CB1) receptor, but was mimicked in magnitude and potency (EC(50)=2.7 microm) by its cannabinoid-inactive enantiomer WIN-3. These findings indicate that WIN-2 exerts both excitatory and inhibitory effects on TG neurons, neither of which appear to be mediated by CB1, CB2 or TRPV1 receptors, but by a novel calcium-dependent mechanism. The ramifications of these results are discussed in relation to our current understanding of cannabinoid/vanilloid interactions with primary sensory neurons.  (+info)

Central effects of the cannabinoid receptor agonist WIN55212-2 on respiratory and cardiovascular regulation in anaesthetised rats. (4/177)

1 The primary aim was to study the central respiratory effects of cannabinoids (CB). To this end, the cannabinoid receptor agonist WIN55212-2 was injected into the cisterna magna of urethane-anaesthetised rats and changes in respiratory parameters were observed. The secondary aim was to observe the centrally elicited cardiovascular actions of WIN55212-2. Involvement of opioid mechanisms in the central effects of WIN55212-2 was also studied. 2 Intracisternal (i.c.) application of WIN55212-2 (1, 3, 10 and 30 microg kg(-1)) dose-dependently decreased the respiratory rate and minute volume. Tidal volume was slightly increased, whereas peak inspiratory flow remained unchanged. In addition, WIN55212-2 increased mean arterial pressure and the plasma noradrenaline concentration and decreased heart rate. 3 I.c. injection of WIN55212-3 (1, 3, 10 and 30 microg kg(-1)), an enantiomer of WIN55212-2 lacking affinity for cannabinoid receptors, elicited no effects. All effects of WIN55212-2 were prevented by the CB1 receptor antagonist SR141716 (2 mg kg(-1) i.v.). I.c. administration of the opioid receptor agonist DAMGO (0.1, 0.3, 1 and 3 microg kg(-1)) markedly lowered the respiratory rate, tidal volume, minute volume and peak inspiratory flow. These effects were attenuated by the opioid receptor antagonist naloxone (0.2 mg kg(-1) i.v.). In contrast, naloxone did not affect the respiratory and cardiovascular effects of i.c. administered WIN55212-2. 4 Our results show that activation of CB1 cannabinoid receptors in the brain stem depresses respiration and enhances sympathetic tone and cardiac vagal tone. Opioid mechanisms are not involved in these central cannabinoid effects.  (+info)

The cannabinomimetic arachidonyl-2-chloroethylamide (ACEA) acts on capsaicin-sensitive TRPV1 receptors but not cannabinoid receptors in rat joints. (5/177)

The vasoactive effects of the synthetic cannabinoid (CB) arachidonyl-2-chloroethylamide (ACEA) was tested in the knee joints of urethane-anaesthetised rats. Experiments were also performed to determine whether these vasomotor responses could be blocked by the selective CB(1) receptor antagonists AM251 (N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole- 3-carboxamide) (10(-9) mol) and AM281 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-c arboxamide) (10(-8) mol), as well as the selective CB(2) receptor antagonist AM630 (6-iodo-2-methyl-1-[2-4(morpholinyl)ethyl]-[1H-indol-3-yl](4-methoxyphenyl)methan one) (10(-8) mol). Peripheral application of ACEA (10(-14)-10(-9) mol) onto the exposed surface of the knee joint capsule caused a dose-dependent increase in synovial blood flow. The dilator action of the CB occurred within 1 min after drug administration and rapidly returned to control levels shortly thereafter. The maximal vasodilator effect of ACEA corresponded to a 30% increase in articular perfusion compared to control levels. The hyperaemic action of ACEA was not significantly altered by coadministration of AM251, AM281 or AM630 (P>0.05; two-way ANOVA). The transient receptor potential channel vanilloid receptor 1 (TRPV(1)) antagonist capsazepine (10(-6) mol) significantly reduced the vasodilator effect of ACEA on joint blood vessels (P=0.002). Furthermore, destruction of unmyelinated and thinly myelinated joint sensory nerves by capsaicin (8-methyl-N-vanillyl-6-nonenamide) treatment also attenuated ACEA responses (P<0.0005). These data clearly demonstrate a vasodilator effect of the cannabinomimetic ACEA on knee joint perfusion. Rather than a classic CB receptor pathway, ACEA exerts its vasomotor influence by acting via TRPV(1) receptors located on the terminal branches of capsaicin-sensitive afferent nerves innervating the joint.  (+info)

Long-lasting increase of alcohol relapse by the cannabinoid receptor agonist WIN 55,212-2 during alcohol deprivation. (6/177)

Alcoholism is characterized by successive relapses. Recent data have shown a cross-talk between the cannabinoid system and ethanol. In this study, male Wistar rats with a limited (30 min sessions), intermittent, and extended background of alcohol operant self-administration were used. The relapse to alcohol after 1 week of alcohol deprivation was evaluated. Two weeks later, the animals were treated with the cannabinoid agonist WIN 55,212-2 (R-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxa zin-6-yl]-1-naphthalenylmethanone mesylate) (0, 0.4, 2.0, and 10.0 mg/kg, s.c.) during a similar alcohol deprivation period, and alcohol relapse during 2 weeks was assessed. A conditioned place preference (CPP) paradigm was used to study the rewarding properties of the cannabinoid agonist. Locomotor activity was also recorded. All doses of WIN 55,212-2 produced aversion in the CPP paradigm. The doses of 2.0 and 10.0 mg/kg resulted in an important suppression of spontaneous locomotor activity and a progressive weight loss during the next 2 weeks. The single alcohol deprivation was followed by a transient increase in their responding for alcohol from a range of 20-24 lever presses at baseline to a range of 38-48 responses in the first and second days (alcohol deprivation effect). However, the administration of WIN 55,212-2 during ethanol deprivation produced similar increased responses for alcohol but in a long-term way (at least over 2 weeks). These findings suggest that noncontingent chronic exposure to cannabinoids during alcohol deprivation can potentiate the relapse into alcohol use, indicating that functional changes in the cannabinoid brain receptor may play a key role in ethanol relapse.  (+info)

2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces rapid actin polymerization in HL-60 cells differentiated into macrophage-like cells. (7/177)

Delta9-Tetrahydrocannabinol, a major psychoactive constituent of marijuana, interacts with specific receptors, i.e. the cannabinoid receptors, thereby eliciting a variety of pharmacological responses. To date, two types of cannabinoid receptors have been identified: the CB1 receptor, which is abundantly expressed in the nervous system, and the CB2 receptor, which is predominantly expressed in the immune system. Previously, we investigated in detail the structure-activity relationship of various cannabinoid receptor ligands and found that 2-AG (2-arachidonoylglycerol) is the most efficacious agonist. We have proposed that 2-AG is the true natural ligand for both the CB1 and CB2 receptors. Despite the potential physiological importance of 2-AG, not much information is available concerning its biological activities towards mammalian tissues and cells. In the present study, we examined the effect of 2-AG on morphology as well as the actin filament system in differentiated HL-60 cells, which express the CB2 receptor. We found that 2-AG induces rapid morphological changes such as the extension of pseudopods. We also found that it provokes a rapid actin polymerization in these cells. Actin polymerization induced by 2-AG was abolished when cells were treated with SR144528, a CB2 receptor antagonist, and pertussis toxin, suggesting that the response was mediated by the CB2 receptor and G(i/o). A phosphoinositide 3-kinase, Rho family small G-proteins and a tyrosine kinase were also suggested to be involved. Reorganization of the actin filament system is known to be indispensable for a variety of cellular events; it is possible that 2-AG plays physiologically essential roles in various inflammatory cells and immune-competent cells by inducing a rapid actin rearrangement.  (+info)

The endocannabinoid system: physiology and pharmacology. (8/177)

The endogenous cannabinoid system is an ubiquitous lipid signalling system that appeared early in evolution and which has important regulatory functions throughout the body in all vertebrates. The main endocannabinoids (endogenous cannabis-like substances) are small molecules derived from arachidonic acid, anandamide (arachidonoylethanolamide) and 2-arachidonoylglycerol. They bind to a family of G-protein-coupled receptors, of which the cannabinoid CB(1) receptor is densely distributed in areas of the brain related to motor control, cognition, emotional responses, motivated behaviour and homeostasis. Outside the brain, the endocannabinoid system is one of the crucial modulators of the autonomic nervous system, the immune system and microcirculation. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and serve as retrograde signalling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters, including dopamine. Endocannabinoids are transported into cells by a specific uptake system and degraded by two well-characterized enzymes, the fatty acid amide hydrolase and the monoacylglycerol lipase. Recent pharmacological advances have led to the synthesis of cannabinoid receptor agonists and antagonists, anandamide uptake blockers and potent, selective inhibitors of endocannabinoid degradation. These new tools have enabled the study of the physiological roles played by the endocannabinoids and have opened up new strategies in the treatment of pain, obesity, neurological diseases including multiple sclerosis, emotional disturbances such as anxiety and other psychiatric disorders including drug addiction. Recent advances have specifically linked the endogenous cannabinoid system to alcoholism, and cannabinoid receptor antagonism now emerges as a promising therapeutic alternative for alcohol dependence and relapse.  (+info)

Cannabinoid receptor agonists are compounds that bind to and activate cannabinoid receptors, which are part of the endocannabinoid system in the human body. These receptors are involved in various physiological processes, including pain modulation, appetite regulation, memory, and mood.

There are two main types of cannabinoid receptors: CB1 receptors, which are primarily found in the brain and central nervous system, and CB2 receptors, which are mainly found in the immune system and peripheral tissues.

Cannabinoid receptor agonists can be classified based on their chemical structure and origin. Some naturally occurring cannabinoids, such as THC (tetrahydrocannabinol) and CBD (cannabidiol), are found in the Cannabis sativa plant and can activate cannabinoid receptors. Synthetic cannabinoids, on the other hand, are human-made compounds designed to mimic or enhance the effects of natural cannabinoids.

Examples of cannabinoid receptor agonists include:

1. THC (tetrahydrocannabinol): The primary psychoactive component of marijuana, THC binds to CB1 receptors and produces feelings of euphoria or "high." It also has analgesic, anti-inflammatory, and appetite-stimulating properties.
2. CBD (cannabidiol): A non-psychoactive compound found in cannabis, CBD has a more complex interaction with the endocannabinoid system. While it does not bind strongly to CB1 or CB2 receptors, it can influence their activity and modulate the effects of other cannabinoids. CBD is known for its potential therapeutic benefits, including anti-inflammatory, analgesic, anxiolytic, and neuroprotective properties.
3. Synthetic cannabinoids: These are human-made compounds designed to mimic or enhance the effects of natural cannabinoids. Examples include dronabinol (Marinol), a synthetic THC used to treat nausea and vomiting in cancer patients, and nabilone (Cesamet), another synthetic THC used to manage pain and nausea in cancer and AIDS patients.
4. CP 55,940: A potent synthetic cannabinoid agonist that binds to both CB1 and CB2 receptors with high affinity. It is used in research to study the endocannabinoid system and its functions.
5. WIN 55,212-2: Another synthetic cannabinoid agonist that binds to both CB1 and CB2 receptors. It is often used in research to investigate the therapeutic potential of cannabinoids.

It's important to note that while some cannabinoid receptor agonists have demonstrated therapeutic benefits, they can also have side effects and potential risks, particularly when used in high doses or without medical supervision. Always consult a healthcare professional before using any cannabinoid-based medication or supplement.

Cannabinoid receptors are a class of cell membrane receptors in the endocannabinoid system that are activated by cannabinoids. The two major types of cannabinoid receptors are CB1 receptors, which are predominantly found in the brain and central nervous system, and CB2 receptors, which are primarily found in the immune system and peripheral tissues. These receptors play a role in regulating various physiological processes such as appetite, pain-sensation, mood, and memory. They can be activated by endocannabinoids (cannabinoids produced naturally in the body), phytocannabinoids (found in cannabis plants), and synthetic cannabinoids.

Cannabinoids are a class of chemical compounds that are produced naturally in the resin of the cannabis plant (also known as marijuana). There are more than 100 different cannabinoids that have been identified, the most well-known of which are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC is the primary psychoactive component of cannabis, meaning it is responsible for the "high" or euphoric feeling that people experience when they use marijuana. CBD, on the other hand, does not have psychoactive effects and is being studied for its potential therapeutic uses in a variety of medical conditions, including pain management, anxiety, and epilepsy.

Cannabinoids work by interacting with the body's endocannabinoid system, which is a complex network of receptors and chemicals that are involved in regulating various physiological processes such as mood, appetite, pain sensation, and memory. When cannabinoids bind to these receptors, they can alter or modulate these processes, leading to potential therapeutic effects.

It's important to note that while some cannabinoids have been shown to have potential medical benefits, marijuana remains a controlled substance in many countries, and its use is subject to legal restrictions. Additionally, the long-term health effects of using marijuana or other forms of cannabis are not fully understood and are the subject of ongoing research.

A cannabinoid receptor, CB1, is a G protein-coupled receptor that is primarily found in the brain and central nervous system. It is one of the two main types of cannabinoid receptors, the other being CB2, and is activated by the endocannabinoid anandamide and the phytocannabinoid Delta-9-tetrahydrocannabinol (THC), which is the primary psychoactive component of cannabis. The activation of CB1 receptors is responsible for many of the psychological effects of cannabis, including euphoria, altered sensory perception, and memory impairment. CB1 receptors are also found in peripheral tissues, such as the adipose tissue, liver, and muscles, where they play a role in regulating energy metabolism, appetite, and pain perception.

A cannabinoid receptor CB2 is a G-protein coupled receptor that is primarily found in the immune system and cells associated with the immune system. They are expressed on the cell surface and are activated by endocannabinoids, plant-derived cannabinoids (phytocannabinoids) like those found in marijuana, and synthetic cannabinoids.

CB2 receptors are involved in a variety of physiological processes including inflammation, pain perception, and immune function. They have been shown to play a role in modulating the release of cytokines, which are signaling molecules that mediate and regulate immunity and inflammation. CB2 receptors may also be found in the brain, although at much lower levels than CB1 receptors.

CB2 receptor agonists have been studied as potential treatments for a variety of conditions including pain management, neuroinflammation, and autoimmune disorders. However, more research is needed to fully understand their therapeutic potential and any associated risks.

Benzoxazines are a class of heterocyclic organic compounds that contain a benzene fused to an oxazine ring. They are known for their diverse chemical and pharmacological properties, including anti-inflammatory, antimicrobial, and antitumor activities. Some benzoxazines also exhibit potential as building blocks in the synthesis of pharmaceuticals and materials. However, it is important to note that specific medical definitions for individual compounds within this class may vary depending on their unique structures and properties.

Cyclohexanols are a class of organic compounds that contain a cyclohexane ring (a six-carbon saturated ring) with a hydroxyl group (-OH) attached to it. The hydroxyl group makes these compounds alcohols, and the cyclohexane ring provides a unique structure that can adopt different conformations.

The presence of the hydroxyl group in cyclohexanols allows them to act as solvents, intermediates in chemical synthesis, and starting materials for the production of other chemicals. They are used in various industries, including pharmaceuticals, agrochemicals, and polymers.

Cyclohexanols can exist in different forms, such as cis- and trans-isomers, depending on the orientation of the hydroxyl group relative to the cyclohexane ring. The physical and chemical properties of these isomers can differ significantly due to their distinct structures and conformations.

Examples of cyclohexanols include cyclohexanol itself (C6H11OH), as well as its derivatives, such as methylcyclohexanol (C7H13OH) and phenylcyclohexanol (C12H15OH).

Naphthalene is not typically referred to as a medical term, but it is a chemical compound with the formula C10H8. It is a white crystalline solid that is aromatic and volatile, and it is known for its distinctive mothball smell. In a medical context, naphthalene is primarily relevant as a potential toxin or irritant.

Naphthalene can be found in some chemical products, such as mothballs and toilet deodorant blocks. Exposure to high levels of naphthalene can cause symptoms such as nausea, vomiting, diarrhea, and headaches. Long-term exposure has been linked to anemia and damage to the liver and nervous system.

In addition, naphthalene is a known environmental pollutant that can be found in air, water, and soil. It is produced by the combustion of fossil fuels and is also released from some industrial processes. Naphthalene has been shown to have toxic effects on aquatic life and may pose a risk to human health if exposure levels are high enough.

Cannabinoid receptor antagonists are a class of compounds that bind to and block cannabinoid receptors, which are specialized proteins found on the surface of certain cells in the body. These receptors play an important role in regulating various physiological processes, including pain perception, appetite regulation, and memory formation.

There are two main types of cannabinoid receptors: CB1 receptors, which are primarily found in the brain and central nervous system, and CB2 receptors, which are mainly found in immune cells and other peripheral tissues.

Cannabinoid receptor antagonists work by preventing the activation of these receptors by natural cannabinoids such as THC (tetrahydrocannabinol), the main psychoactive component of marijuana. By blocking the effects of THC, cannabinoid receptor antagonists can be used to treat conditions that are exacerbated by THC, such as substance use disorders and psychosis.

One example of a cannabinoid receptor antagonist is rimonabant, which was approved in Europe for the treatment of obesity but was later withdrawn from the market due to concerns about psychiatric side effects. Other cannabinoid receptor antagonists are currently being investigated for their potential therapeutic uses, including the treatment of pain, inflammation, and neurodegenerative disorders.

Dronabinol is a synthetic form of delta-9-tetrahydrocannabinol (THC), which is the main psychoactive compound found in cannabis. It is approved by the US Food and Drug Administration (FDA) for the treatment of nausea and vomiting caused by chemotherapy in cancer patients, as well as to stimulate appetite and weight gain in patients with AIDS wasting syndrome.

Dronabinol is available in capsule form and is typically taken two to three times a day, depending on the prescribed dosage. It may take several days or even weeks of regular use before the full therapeutic effects are achieved.

Like cannabis, dronabinol can cause psychoactive effects such as euphoria, altered mood, and impaired cognitive function. Therefore, it is important to follow the prescribing instructions carefully and avoid driving or operating heavy machinery while taking this medication. Common side effects of dronabinol include dizziness, drowsiness, dry mouth, and difficulty with coordination.

Cannabinoid receptor modulators are a class of compounds that interact with and modify the function of cannabinoid receptors, which are part of the endocannabinoid system in the human body. These receptors play a role in regulating various physiological processes such as pain, mood, memory, appetite, and immunity.

There are two main types of cannabinoid receptors: CB1 receptors, which are primarily found in the brain and central nervous system, and CB2 receptors, which are mainly found in the immune system and peripheral tissues. Cannabinoid receptor modulators can be classified into three categories based on their effects on these receptors:

1. Agonists: These compounds bind to and activate cannabinoid receptors, leading to a range of effects such as pain relief, anti-inflammation, and mood enhancement. Examples include THC (tetrahydrocannabinol), the psychoactive component of marijuana, and synthetic cannabinoids like dronabinol (Marinol) and nabilone (Cesamet).
2. Antagonists: These compounds bind to cannabinoid receptors but do not activate them, instead blocking or reducing the effects of agonist compounds. Examples include rimonabant (Acomplia), which was withdrawn from the market due to psychiatric side effects, and SR141716A.
3. Inverse Agonists: These compounds bind to cannabinoid receptors and produce effects opposite to those of agonist compounds. Examples include CBD (cannabidiol), a non-psychoactive component of marijuana that has anti-inflammatory, anxiolytic, and neuroprotective properties.

Cannabinoid receptor modulators have potential therapeutic applications in various medical conditions such as chronic pain, multiple sclerosis, epilepsy, cancer, and mental health disorders. However, further research is needed to fully understand their mechanisms of action and potential side effects.

Drug receptors are specific protein molecules found on the surface of cells, to which drugs can bind. These receptors are part of the cell's communication system and are responsible for responding to neurotransmitters, hormones, and other signaling molecules in the body. When a drug binds to its corresponding receptor, it can alter the receptor's function and trigger a cascade of intracellular events that ultimately lead to a biological response.

Drug receptors can be classified into several types based on their function, including:

1. G protein-coupled receptors (GPCRs): These are the largest family of drug receptors and are involved in various physiological processes such as vision, olfaction, neurotransmission, and hormone signaling. They activate intracellular signaling pathways through heterotrimeric G proteins.
2. Ion channel receptors: These receptors form ion channels that allow the flow of ions across the cell membrane when activated. They are involved in rapid signal transduction and can be directly gated by ligands or indirectly through G protein-coupled receptors.
3. Enzyme-linked receptors: These receptors have an intracellular domain that functions as an enzyme, activating intracellular signaling pathways when bound to a ligand. Examples include receptor tyrosine kinases and receptor serine/threonine kinases.
4. Nuclear receptors: These receptors are located in the nucleus and function as transcription factors, regulating gene expression upon binding to their ligands.

Understanding drug receptors is crucial for developing new drugs and predicting their potential therapeutic and adverse effects. By targeting specific receptors, drugs can modulate cellular responses and produce desired pharmacological actions.

I'm sorry for any confusion, but "Morpholines" is not a medical term. It is a chemical term that refers to a class of heterocyclic organic compounds containing one nitrogen atom and one oxygen atom in the ring. They are widely used as intermediates in the synthesis of various pharmaceuticals, agrochemicals, and dyes. If you have any questions about a medical issue or term, I'd be happy to try to help answer those for you!

Endocannabinoids are naturally occurring compounds in the body that bind to cannabinoid receptors, which are found in various tissues and organs throughout the body. These compounds play a role in regulating many physiological processes, including appetite, mood, pain sensation, and memory. They are similar in structure to the active components of cannabis (marijuana), called phytocannabinoids, such as THC (tetrahydrocannabinol) and CBD (cannabidiol). However, endocannabinoids are produced by the body itself, whereas phytocannabinoids come from the cannabis plant. The two most well-known endocannabinoids are anandamide and 2-arachidonoylglycerol (2-AG).

Pyrazoles are heterocyclic aromatic organic compounds that contain a six-membered ring with two nitrogen atoms at positions 1 and 2. The chemical structure of pyrazoles consists of a pair of nitrogen atoms adjacent to each other in the ring, which makes them unique from other azole heterocycles such as imidazoles or triazoles.

Pyrazoles have significant biological activities and are found in various pharmaceuticals, agrochemicals, and natural products. Some pyrazole derivatives exhibit anti-inflammatory, analgesic, antipyretic, antimicrobial, antiviral, antifungal, and anticancer properties.

In the medical field, pyrazoles are used in various drugs to treat different conditions. For example, celecoxib (Celebrex) is a selective COX-2 inhibitor used for pain relief and inflammation reduction in arthritis patients. It contains a pyrazole ring as its core structure. Similarly, febuxostat (Uloric) is a medication used to treat gout, which also has a pyrazole moiety.

Overall, pyrazoles are essential compounds with significant medical applications and potential for further development in drug discovery and design.

I'm sorry for any confusion, but "Polyunsaturated Alkamides" is not a widely recognized medical term or concept. It seems to be a combination of two different terms: "polyunsaturated" which relates to fatty acid chemistry, and "alkamides" which are a type of compound found in certain plants.

1. Polyunsaturated: This term refers to fatty acids that have multiple double bonds in their carbon chain. These fatty acids are essential to the human diet and are commonly found in foods like fish, nuts, and seeds. They are often referred to as Omega-3 or Omega-6 fatty acids.

2. Alkamides: These are a type of compound found in some plants, including Echinacea species. They have been studied for their potential biological activities, such as anti-inflammatory and immunomodulatory effects.

Without more context, it's difficult to provide a precise definition or medical interpretation of "Polyunsaturated Alkamides." If you have more information about how these terms are being used together, I'd be happy to try to provide a more specific answer.

Piperidines are not a medical term per se, but they are a class of organic compounds that have important applications in the pharmaceutical industry. Medically relevant piperidines include various drugs such as some antihistamines, antidepressants, and muscle relaxants.

A piperidine is a heterocyclic amine with a six-membered ring containing five carbon atoms and one nitrogen atom. The structure can be described as a cyclic secondary amine. Piperidines are found in some natural alkaloids, such as those derived from the pepper plant (Piper nigrum), which gives piperidines their name.

In a medical context, it is more common to encounter specific drugs that belong to the class of piperidines rather than the term itself.

I'm sorry for any confusion, but "bornanes" is not a medical term or concept. It is a chemical term that refers to a class of compounds called bornane derivatives, which are structurally related to the naturally occurring compound bornane. These compounds have various uses in chemistry and materials science, but they do not have specific relevance to medicine or human health.

Arachidonic acids are a type of polyunsaturated fatty acid that is primarily found in the phospholipids of cell membranes. They contain 20 carbon atoms and four double bonds (20:4n-6), with the first double bond located at the sixth carbon atom from the methyl end.

Arachidonic acids are derived from linoleic acid, an essential fatty acid that cannot be synthesized by the human body and must be obtained through dietary sources such as meat, fish, and eggs. Once ingested, linoleic acid is converted to arachidonic acid in a series of enzymatic reactions.

Arachidonic acids play an important role in various physiological processes, including inflammation, immune response, and cell signaling. They serve as precursors for the synthesis of eicosanoids, which are signaling molecules that include prostaglandins, thromboxanes, and leukotrienes. These eicosanoids have diverse biological activities, such as modulating blood flow, platelet aggregation, and pain perception, among others.

However, excessive production of arachidonic acid-derived eicosanoids has been implicated in various pathological conditions, including inflammation, atherosclerosis, and cancer. Therefore, the regulation of arachidonic acid metabolism is an important area of research for the development of new therapeutic strategies.

Analgesics are a class of drugs that are used to relieve pain. They work by blocking the transmission of pain signals in the nervous system, allowing individuals to manage their pain levels more effectively. There are many different types of analgesics available, including both prescription and over-the-counter options. Some common examples include acetaminophen (Tylenol), ibuprofen (Advil or Motrin), and opioids such as morphine or oxycodone.

The choice of analgesic will depend on several factors, including the type and severity of pain being experienced, any underlying medical conditions, potential drug interactions, and individual patient preferences. It is important to use these medications as directed by a healthcare provider, as misuse or overuse can lead to serious side effects and potential addiction.

In addition to their pain-relieving properties, some analgesics may also have additional benefits such as reducing inflammation (like in the case of nonsteroidal anti-inflammatory drugs or NSAIDs) or causing sedation (as with certain opioids). However, it is essential to weigh these potential benefits against the risks and side effects associated with each medication.

When used appropriately, analgesics can significantly improve a person's quality of life by helping them manage their pain effectively and allowing them to engage in daily activities more comfortably.

Glycerides are esters formed from glycerol and one, two, or three fatty acids. They include monoglycerides (one fatty acid), diglycerides (two fatty acids), and triglycerides (three fatty acids). Triglycerides are the main constituents of natural fats and oils, and they are a major form of energy storage in animals and plants. High levels of triglycerides in the blood, also known as hypertriglyceridemia, can increase the risk of heart disease and stroke.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Amidohydrolases are a class of enzymes that catalyze the hydrolysis of amides and related compounds, resulting in the formation of an acid and an alcohol. This reaction is also known as amide hydrolysis or amide bond cleavage. Amidohydrolases play important roles in various biological processes, including the metabolism of xenobiotics (foreign substances) and endogenous compounds (those naturally produced within an organism).

The term "amidohydrolase" is a broad one that encompasses several specific types of enzymes, such as proteases, esterases, lipases, and nitrilases. These enzymes have different substrate specificities and catalytic mechanisms but share the common ability to hydrolyze amide bonds.

Proteases, for example, are a major group of amidohydrolases that specifically cleave peptide bonds in proteins. They are involved in various physiological processes, such as protein degradation, digestion, and regulation of biological pathways. Esterases and lipases hydrolyze ester bonds in various substrates, including lipids and other organic compounds. Nitrilases convert nitriles into carboxylic acids and ammonia by cleaving the nitrile bond (C≡N) through hydrolysis.

Amidohydrolases are found in various organisms, from bacteria to humans, and have diverse applications in industry, agriculture, and medicine. For instance, they can be used for the production of pharmaceuticals, biofuels, detergents, and other chemicals. Additionally, inhibitors of amidohydrolases can serve as therapeutic agents for treating various diseases, such as cancer, viral infections, and neurodegenerative disorders.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

Cannabidiol (CBD) is a chemical compound found in the Cannabis sativa plant, also known as cannabis or marijuana. It is one of many such compounds, known as cannabinoids, that are found in the plant. Unlike tetrahydrocannabinol (THC), which is the main psychoactive component of cannabis and is responsible for the "high" associated with its use, CBD does not have psychoactive effects.

CBD has been studied for its potential therapeutic uses in a variety of medical conditions, including epilepsy, anxiety, and chronic pain. It is available in various forms, such as oils, capsules, and topical creams, and can be taken orally or applied to the skin. However, it is important to note that the use of CBD is not currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of any medical condition, except for the treatment of certain forms of epilepsy. As with any medication or supplement, it is important to talk to your doctor before using CBD, especially if you are taking other medications or have underlying health conditions.

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. It is a complex phenomenon that can result from various stimuli, such as thermal, mechanical, or chemical irritation, and it can be acute or chronic. The perception of pain involves the activation of specialized nerve cells called nociceptors, which transmit signals to the brain via the spinal cord. These signals are then processed in different regions of the brain, leading to the conscious experience of pain. It's important to note that pain is a highly individual and subjective experience, and its perception can vary widely among individuals.

Calcium channel blockers (CCBs) are a class of medications that work by inhibiting the influx of calcium ions into cardiac and smooth muscle cells. This action leads to relaxation of the muscles, particularly in the blood vessels, resulting in decreased peripheral resistance and reduced blood pressure. Calcium channel blockers also have anti-arrhythmic effects and are used in the management of various cardiovascular conditions such as hypertension, angina, and certain types of arrhythmias.

Calcium channel blockers can be further classified into two main categories based on their chemical structure: dihydropyridines (e.g., nifedipine, amlodipine) and non-dihydropyridines (e.g., verapamil, diltiazem). Dihydropyridines are more selective for vascular smooth muscle and have a greater effect on blood pressure than heart rate or conduction. Non-dihydropyridines have a more significant impact on cardiac conduction and contractility, in addition to their vasodilatory effects.

It is important to note that calcium channel blockers may interact with other medications and should be used under the guidance of a healthcare professional. Potential side effects include dizziness, headache, constipation, and peripheral edema.

A drug interaction is the effect of combining two or more drugs, or a drug and another substance (such as food or alcohol), which can alter the effectiveness or side effects of one or both of the substances. These interactions can be categorized as follows:

1. Pharmacodynamic interactions: These occur when two or more drugs act on the same target organ or receptor, leading to an additive, synergistic, or antagonistic effect. For example, taking a sedative and an antihistamine together can result in increased drowsiness due to their combined depressant effects on the central nervous system.
2. Pharmacokinetic interactions: These occur when one drug affects the absorption, distribution, metabolism, or excretion of another drug. For example, taking certain antibiotics with grapefruit juice can increase the concentration of the antibiotic in the bloodstream, leading to potential toxicity.
3. Food-drug interactions: Some drugs may interact with specific foods, affecting their absorption, metabolism, or excretion. An example is the interaction between warfarin (a blood thinner) and green leafy vegetables, which can increase the risk of bleeding due to enhanced vitamin K absorption from the vegetables.
4. Drug-herb interactions: Some herbal supplements may interact with medications, leading to altered drug levels or increased side effects. For instance, St. John's Wort can decrease the effectiveness of certain antidepressants and oral contraceptives by inducing their metabolism.
5. Drug-alcohol interactions: Alcohol can interact with various medications, causing additive sedative effects, impaired judgment, or increased risk of liver damage. For example, combining alcohol with benzodiazepines or opioids can lead to dangerous levels of sedation and respiratory depression.

It is essential for healthcare providers and patients to be aware of potential drug interactions to minimize adverse effects and optimize treatment outcomes.

"Wistar rats" are a strain of albino rats that are widely used in laboratory research. They were developed at the Wistar Institute in Philadelphia, USA, and were first introduced in 1906. Wistar rats are outbred, which means that they are genetically diverse and do not have a fixed set of genetic characteristics like inbred strains.

Wistar rats are commonly used as animal models in biomedical research because of their size, ease of handling, and relatively low cost. They are used in a wide range of research areas, including toxicology, pharmacology, nutrition, cancer, cardiovascular disease, and behavioral studies. Wistar rats are also used in safety testing of drugs, medical devices, and other products.

Wistar rats are typically larger than many other rat strains, with males weighing between 500-700 grams and females weighing between 250-350 grams. They have a lifespan of approximately 2-3 years. Wistar rats are also known for their docile and friendly nature, making them easy to handle and work with in the laboratory setting.

Monoacylglycerol lipases (MAGLs) are a type of enzyme that play a role in the metabolism of lipids, specifically by breaking down monoacylglycerols into glycerol and free fatty acids. Monoacylglycerols are formed during the digestion of dietary fats and are also produced endogenously as a result of the breakdown of complex lipids.

MAGLs are widely distributed throughout the body, but are particularly abundant in tissues that utilize large amounts of fatty acids for energy, such as the liver, heart, and skeletal muscle. In addition to their role in lipid metabolism, MAGLs have been implicated in various physiological processes, including inflammation, pain perception, and cancer.

Inhibition of MAGL activity has been proposed as a potential therapeutic strategy for the treatment of various diseases, including obesity, diabetes, and neurodegenerative disorders. However, further research is needed to fully understand the role of MAGLs in these processes and to determine the safety and efficacy of MAGL inhibitors as drugs.

Synaptic transmission is the process by which a neuron communicates with another cell, such as another neuron or a muscle cell, across a junction called a synapse. It involves the release of neurotransmitters from the presynaptic terminal of the neuron, which then cross the synaptic cleft and bind to receptors on the postsynaptic cell, leading to changes in the electrical or chemical properties of the target cell. This process is critical for the transmission of signals within the nervous system and for controlling various physiological functions in the body.

Purinergic P1 receptor agonists are substances that bind to and activate purinergic P1 receptors, which are a type of G protein-coupled receptor found in many tissues throughout the body. These receptors are activated by endogenous nucleotides such as adenosine and its metabolites.

Purinergic P1 receptors include four subtypes: A1, A2A, A2B, and A3. Each of these subtypes has distinct signaling pathways and physiological roles. For example, A1 receptor activation can lead to vasodilation, bradycardia, and anti-inflammatory effects, while A2A receptor activation can increase cyclic AMP levels and have anti-inflammatory effects.

Purinergic P1 receptor agonists are used in various therapeutic applications, including as cardiovascular drugs, antiplatelet agents, and anti-inflammatory agents. Some examples of purinergic P1 receptor agonists include adenosine, regadenoson, and dipyridamole.

It's important to note that the use of these substances should be under medical supervision due to their potential side effects and interactions with other medications.

Pain measurement, in a medical context, refers to the quantification or evaluation of the intensity and/or unpleasantness of a patient's subjective pain experience. This is typically accomplished through the use of standardized self-report measures such as numerical rating scales (NRS), visual analog scales (VAS), or categorical scales (mild, moderate, severe). In some cases, physiological measures like heart rate, blood pressure, and facial expressions may also be used to supplement self-reported pain ratings. The goal of pain measurement is to help healthcare providers better understand the nature and severity of a patient's pain in order to develop an effective treatment plan.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

Serotonin receptor agonists are a class of medications that bind to and activate serotonin receptors in the body, mimicking the effects of the neurotransmitter serotonin. These drugs can have various effects depending on which specific serotonin receptors they act upon. Some serotonin receptor agonists are used to treat conditions such as migraines, cluster headaches, and Parkinson's disease, while others may be used to stimulate appetite or reduce anxiety. It is important to note that some serotonin receptor agonists can have serious side effects, particularly when taken in combination with other medications that affect serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs). This can lead to a condition called serotonin syndrome, which is characterized by symptoms such as agitation, confusion, rapid heart rate, high blood pressure, and muscle stiffness.

Neurons, also known as nerve cells or neurocytes, are specialized cells that constitute the basic unit of the nervous system. They are responsible for receiving, processing, and transmitting information and signals within the body. Neurons have three main parts: the dendrites, the cell body (soma), and the axon. The dendrites receive signals from other neurons or sensory receptors, while the axon transmits these signals to other neurons, muscles, or glands. The junction between two neurons is called a synapse, where neurotransmitters are released to transmit the signal across the gap (synaptic cleft) to the next neuron. Neurons vary in size, shape, and structure depending on their function and location within the nervous system.

Dopamine agonists are a class of medications that mimic the action of dopamine, a neurotransmitter in the brain that regulates movement, emotion, motivation, and reinforcement of rewarding behaviors. These medications bind to dopamine receptors in the brain and activate them, leading to an increase in dopaminergic activity.

Dopamine agonists are used primarily to treat Parkinson's disease, a neurological disorder characterized by motor symptoms such as tremors, rigidity, bradykinesia (slowness of movement), and postural instability. By increasing dopaminergic activity in the brain, dopamine agonists can help alleviate some of these symptoms.

Examples of dopamine agonists include:

1. Pramipexole (Mirapex)
2. Ropinirole (Requip)
3. Rotigotine (Neupro)
4. Apomorphine (Apokyn)

Dopamine agonists may also be used off-label to treat other conditions, such as restless legs syndrome or certain types of dopamine-responsive dystonia. However, these medications can have significant side effects, including nausea, dizziness, orthostatic hypotension, compulsive behaviors (such as gambling, shopping, or sexual addiction), and hallucinations. Therefore, they should be used with caution and under the close supervision of a healthcare provider.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Cannabinol (CBN) is a chemical compound found in cannabis plants. It is one of the many cannabinoids that can be extracted from the plant, but it is not as well-known or widely studied as tetrahydrocannabinol (THC) and cannabidiol (CBD).

CBN is formed when THC degrades over time due to exposure to air, heat, and light. As a result, older or improperly stored cannabis may contain higher levels of CBN than fresh or properly stored cannabis.

CBN has been shown to have some therapeutic potential, including as a sedative, an anti-inflammatory, and an appetite stimulant. However, more research is needed to fully understand its effects and potential medical uses. It's worth noting that CBN does not produce the psychoactive effects associated with THC.

Cannabis is a plant genus that includes three species: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. It contains psychoactive compounds called cannabinoids, the most notable of which is delta-9-tetrahydrocannabinol (THC), which produces the "high" associated with marijuana use.

Cannabis sativa and Cannabis indica are primarily used for recreational and medicinal purposes, while Cannabis ruderalis has a lower THC content and is mainly used for industrial purposes, such as hemp fiber production.

Medicinally, cannabis is used to treat various conditions, including pain, nausea, and loss of appetite associated with cancer and HIV/AIDS, multiple sclerosis, epilepsy, and post-traumatic stress disorder (PTSD), among others. However, its use remains controversial due to its psychoactive effects and potential for abuse. Its legal status varies widely around the world, ranging from outright prohibition to decriminalization or full legalization for medical and/or recreational purposes.

Serotonin 5-HT1 Receptor Agonists are a class of compounds that bind to and activate the serotonin 5-HT1 receptors, which are G protein-coupled receptors found in the central and peripheral nervous systems. These receptors play important roles in regulating various physiological functions, including neurotransmission, vasoconstriction, and hormone secretion.

Serotonin 5-HT1 Receptor Agonists are used in medical therapy to treat a variety of conditions, such as migraines, cluster headaches, depression, anxiety, and insomnia. Some examples of Serotonin 5-HT1 Receptor Agonists include sumatriptan, rizatriptan, zolmitriptan, naratriptan, and frovatriptan, which are used to treat migraines and cluster headaches by selectively activating the 5-HT1B/1D receptors in cranial blood vessels and sensory nerves.

Other Serotonin 5-HT1 Receptor Agonists, such as buspirone, are used to treat anxiety disorders and depression by acting on the 5-HT1A receptors in the brain. These drugs work by increasing serotonergic neurotransmission, which helps to regulate mood, cognition, and behavior.

Overall, Serotonin 5-HT1 Receptor Agonists are a valuable class of drugs that have shown efficacy in treating various neurological and psychiatric conditions. However, like all medications, they can have side effects and potential drug interactions, so it is important to use them under the guidance of a healthcare professional.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Animal disease models are specialized animals, typically rodents such as mice or rats, that have been genetically engineered or exposed to certain conditions to develop symptoms and physiological changes similar to those seen in human diseases. These models are used in medical research to study the pathophysiology of diseases, identify potential therapeutic targets, test drug efficacy and safety, and understand disease mechanisms.

The genetic modifications can include knockout or knock-in mutations, transgenic expression of specific genes, or RNA interference techniques. The animals may also be exposed to environmental factors such as chemicals, radiation, or infectious agents to induce the disease state.

Examples of animal disease models include:

1. Mouse models of cancer: Genetically engineered mice that develop various types of tumors, allowing researchers to study cancer initiation, progression, and metastasis.
2. Alzheimer's disease models: Transgenic mice expressing mutant human genes associated with Alzheimer's disease, which exhibit amyloid plaque formation and cognitive decline.
3. Diabetes models: Obese and diabetic mouse strains like the NOD (non-obese diabetic) or db/db mice, used to study the development of type 1 and type 2 diabetes, respectively.
4. Cardiovascular disease models: Atherosclerosis-prone mice, such as ApoE-deficient or LDLR-deficient mice, that develop plaque buildup in their arteries when fed a high-fat diet.
5. Inflammatory bowel disease models: Mice with genetic mutations affecting intestinal barrier function and immune response, such as IL-10 knockout or SAMP1/YitFc mice, which develop colitis.

Animal disease models are essential tools in preclinical research, but it is important to recognize their limitations. Differences between species can affect the translatability of results from animal studies to human patients. Therefore, researchers must carefully consider the choice of model and interpret findings cautiously when applying them to human diseases.

Serotonin 5-HT2 receptor agonists are a class of compounds that bind to and activate the serotonin 5-HT2 receptors, which are a type of G protein-coupled receptor found in the central and peripheral nervous systems. These receptors play important roles in various physiological processes, including neurotransmission, vasoconstriction, and smooth muscle contraction.

Serotonin 5-HT2 receptor agonists can produce a range of effects depending on the specific subtype of receptor they activate. For example, activation of 5-HT2A receptors has been associated with hallucinogenic effects, while activation of 5-HT2B receptors has been linked to cardiac valvulopathy.

These drugs are used in a variety of clinical settings, including the treatment of psychiatric disorders such as depression and schizophrenia, migraine headaches, and cluster headaches. Examples of serotonin 5-HT2 receptor agonists include LSD, psilocybin, ergotamine, and sumatriptan.

Adenosine A1 receptor agonists are medications or substances that bind to and activate the adenosine A1 receptors, which are found on the surface of certain cells in the body, including those in the heart, brain, and other organs.

Adenosine is a naturally occurring molecule in the body that helps regulate various physiological processes, such as cardiovascular function and neurotransmission. The adenosine A1 receptor plays an important role in modulating the activity of the heart, including reducing heart rate and lowering blood pressure.

Adenosine A1 receptor agonists are used clinically to treat certain medical conditions, such as supraventricular tachycardia (a rapid heart rhythm originating from above the ventricles), and to prevent cerebral vasospasm (narrowing of blood vessels in the brain) following subarachnoid hemorrhage.

Examples of adenosine A1 receptor agonists include adenosine, regadenoson, and capadenoson. These medications work by mimicking the effects of naturally occurring adenosine on the A1 receptors, leading to a decrease in heart rate and blood pressure.

It's important to note that adenosine A1 receptor agonists can have side effects, such as chest pain, shortness of breath, and flushing, which are usually transient and mild. However, they should be used with caution and under the supervision of a healthcare professional, as they can also have more serious side effects in certain individuals.

A ligand, in the context of biochemistry and medicine, is a molecule that binds to a specific site on a protein or a larger biomolecule, such as an enzyme or a receptor. This binding interaction can modify the function or activity of the target protein, either activating it or inhibiting it. Ligands can be small molecules, like hormones or neurotransmitters, or larger structures, like antibodies. The study of ligand-protein interactions is crucial for understanding cellular processes and developing drugs, as many therapeutic compounds function by binding to specific targets within the body.

Indole is not strictly a medical term, but it is a chemical compound that can be found in the human body and has relevance to medical and biological research. Indoles are organic compounds that contain a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring.

In the context of medicine, indoles are particularly relevant due to their presence in certain hormones and other biologically active molecules. For example, the neurotransmitter serotonin contains an indole ring, as does the hormone melatonin. Indoles can also be found in various plant-based foods, such as cruciferous vegetables (e.g., broccoli, kale), and have been studied for their potential health benefits.

Some indoles, like indole-3-carbinol and diindolylmethane, are found in these vegetables and can have anti-cancer properties by modulating estrogen metabolism, reducing inflammation, and promoting cell death (apoptosis) in cancer cells. However, it is essential to note that further research is needed to fully understand the potential health benefits and risks associated with indoles.

Opioid mu receptors, also known as mu-opioid receptors (MORs), are a type of G protein-coupled receptor that binds to opioids, a class of chemicals that include both natural and synthetic painkillers. These receptors are found in the brain, spinal cord, and gastrointestinal tract, and play a key role in mediating the effects of opioid drugs such as morphine, heroin, and oxycodone.

MORs are involved in pain modulation, reward processing, respiratory depression, and physical dependence. Activation of MORs can lead to feelings of euphoria, decreased perception of pain, and slowed breathing. Prolonged activation of these receptors can also result in tolerance, where higher doses of the drug are required to achieve the same effect, and dependence, where withdrawal symptoms occur when the drug is discontinued.

MORs have three main subtypes: MOR-1, MOR-2, and MOR-3, with MOR-1 being the most widely studied and clinically relevant. Selective agonists for MOR-1, such as fentanyl and sufentanil, are commonly used in anesthesia and pain management. However, the abuse potential and risk of overdose associated with these drugs make them a significant public health concern.

A radioligand assay is a type of in vitro binding assay used in molecular biology and pharmacology to measure the affinity and quantity of a ligand (such as a drug or hormone) to its specific receptor. In this technique, a small amount of a radioactively labeled ligand, also known as a radioligand, is introduced to a sample containing the receptor of interest. The radioligand binds competitively with other unlabeled ligands present in the sample for the same binding site on the receptor. After allowing sufficient time for binding, the reaction is stopped, and the amount of bound radioligand is measured using a technique such as scintillation counting. The data obtained from this assay can be used to determine the dissociation constant (Kd) and maximum binding capacity (Bmax) of the receptor-ligand interaction, which are important parameters in understanding the pharmacological properties of drugs and other ligands.

GABA (gamma-aminobutyric acid) agonists are substances that bind to and activate GABA receptors in the brain, mimicking the actions of GABA, which is the primary inhibitory neurotransmitter in the central nervous system. These agents can produce various effects such as sedation, anxiolysis, muscle relaxation, and anticonvulsant activity by enhancing the inhibitory tone in the brain. They are used clinically to treat conditions such as anxiety disorders, seizures, and muscle spasticity. Examples of GABA agonists include benzodiazepines, barbiturates, and certain non-benzodiazepine hypnotics.

Opioid receptors, also known as opiate receptors, are a type of G protein-coupled receptor found in the nervous system and other tissues. They are activated by endogenous opioid peptides, as well as exogenous opiates and opioids. There are several subtypes of opioid receptors, including mu, delta, and kappa.

Kappa opioid receptors (KORs) are a subtype of opioid receptor that are widely distributed throughout the body, including in the brain, spinal cord, and gastrointestinal tract. They are activated by endogenous opioid peptides such as dynorphins, as well as by synthetic and semi-synthetic opioids such as salvinorin A and U-69593.

KORs play a role in the modulation of pain, mood, and addictive behaviors. Activation of KORs has been shown to produce analgesic effects, but can also cause dysphoria, sedation, and hallucinations. KOR agonists have potential therapeutic uses for the treatment of pain, addiction, and other disorders, but their use is limited by their side effects.

It's important to note that opioid receptors and their ligands (drugs or endogenous substances that bind to them) are complex systems with many different actions and effects in the body. The specific effects of KOR activation depend on a variety of factors, including the location and density of the receptors, the presence of other receptors and signaling pathways, and the dose and duration of exposure to the ligand.

Adenosine A2 receptor agonists are pharmaceutical agents that bind to and activate the A2 subtype of adenosine receptors, which are G-protein coupled receptors found in various tissues throughout the body. Activation of these receptors leads to a variety of physiological effects, including vasodilation, increased coronary blood flow, and inhibition of platelet aggregation.

A2 receptor agonists have been studied for their potential therapeutic benefits in several medical conditions, such as:

1. Heart failure: A2 receptor agonists can improve cardiac function and reduce symptoms in patients with heart failure by increasing coronary blood flow and reducing oxygen demand.
2. Atrial fibrillation: These agents have been shown to terminate or prevent atrial fibrillation, a common abnormal heart rhythm disorder, through their effects on the electrical properties of cardiac cells.
3. Asthma and COPD: A2 receptor agonists can help relax airway smooth muscle and reduce inflammation in patients with asthma and chronic obstructive pulmonary disease (COPD).
4. Pain management: Some A2 receptor agonists have been found to have analgesic properties, making them potential candidates for pain relief in various clinical settings.

Examples of A2 receptor agonists include regadenoson, which is used as a pharmacological stress agent during myocardial perfusion imaging, and dipyridamole, which is used to prevent blood clots in patients with certain heart conditions. However, it's important to note that these agents can have side effects, such as hypotension, bradycardia, and bronchoconstriction, so their use must be carefully monitored and managed by healthcare professionals.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

CHO cells, or Chinese Hamster Ovary cells, are a type of immortalized cell line that are commonly used in scientific research and biotechnology. They were originally derived from the ovaries of a female Chinese hamster (Cricetulus griseus) in the 1950s.

CHO cells have several characteristics that make them useful for laboratory experiments. They can grow and divide indefinitely under appropriate conditions, which allows researchers to culture large quantities of them for study. Additionally, CHO cells are capable of expressing high levels of recombinant proteins, making them a popular choice for the production of therapeutic drugs, vaccines, and other biologics.

In particular, CHO cells have become a workhorse in the field of biotherapeutics, with many approved monoclonal antibody-based therapies being produced using these cells. The ability to genetically modify CHO cells through various methods has further expanded their utility in research and industrial applications.

It is important to note that while CHO cells are widely used in scientific research, they may not always accurately represent human cell behavior or respond to drugs and other compounds in the same way as human cells do. Therefore, results obtained using CHO cells should be validated in more relevant systems when possible.

GABA-A receptor agonists are substances that bind to and activate GABA-A receptors, which are ligand-gated ion channels found in the central nervous system. GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the brain, and its activation via GABA-A receptors results in hyperpolarization of neurons and reduced neuronal excitability.

GABA-A receptor agonists can be classified into two categories: GABAergic compounds and non-GABAergic compounds. GABAergic compounds, such as muscimol and isoguvacine, are structurally similar to GABA and directly activate the receptors. Non-GABAergic compounds, on the other hand, include benzodiazepines, barbiturates, and neurosteroids, which allosterically modulate the receptor's affinity for GABA, thereby enhancing its inhibitory effects.

These agents are used in various clinical settings to treat conditions such as anxiety, insomnia, seizures, and muscle spasticity. However, they can also produce adverse effects, including sedation, cognitive impairment, respiratory depression, and physical dependence, particularly when used at high doses or for prolonged periods.

'Animal behavior' refers to the actions or responses of animals to various stimuli, including their interactions with the environment and other individuals. It is the study of the actions of animals, whether they are instinctual, learned, or a combination of both. Animal behavior includes communication, mating, foraging, predator avoidance, and social organization, among other things. The scientific study of animal behavior is called ethology. This field seeks to understand the evolutionary basis for behaviors as well as their physiological and psychological mechanisms.

GABA-B receptor agonists are substances that bind to and activate GABA-B receptors, which are G protein-coupled receptors found in the central nervous system. GABA (gamma-aminobutyric acid) is the primary inhibitory neurotransmitter in the brain, and its activation leads to decreased neuronal excitability.

GABA-B receptor agonists can produce various effects on the body, including sedation, anxiolysis, analgesia, and anticonvulsant activity. Some examples of GABA-B receptor agonists include baclofen, gabapentin, and pregabalin. These drugs are used in the treatment of a variety of medical conditions, such as muscle spasticity, epilepsy, and neuropathic pain.

It's important to note that while GABA-B receptor agonists can have therapeutic effects, they can also produce side effects such as dizziness, weakness, and respiratory depression, especially at high doses or in overdose situations. Therefore, these drugs should be used with caution and under the supervision of a healthcare provider.

Serotonin 5-HT4 receptor agonists are a class of medications that selectively bind to and activate serotonin 5-HT4 receptors. These receptors are found in various parts of the body, including the gastrointestinal tract, brain, and heart.

When serotonin 5-HT4 receptor agonists bind to these receptors, they stimulate a range of physiological responses, such as increasing gastrointestinal motility, improving cognitive function, and regulating cardiac function. These drugs have been used in the treatment of various conditions, including constipation, irritable bowel syndrome, and depression.

Examples of serotonin 5-HT4 receptor agonists include prucalopride, cisapride, mosapride, and tegaserod. However, some of these drugs have been withdrawn from the market due to safety concerns, such as cardiac arrhythmias. Therefore, it is essential to use these medications under the close supervision of a healthcare provider.

Drug inverse agonism is a property of certain drugs that can bind to and stabilize the inactive conformation of a G protein-coupled receptor (GPCR) or other type of receptor. This results in a reduction of the receptor's basal activity, which is the level of signaling that occurs in the absence of an agonist ligand.

An inverse agonist drug can have the opposite effect of an agonist drug, which binds to and stabilizes the active conformation of a receptor and increases its signaling activity. An inverse agonist drug can also have a greater effect than a simple antagonist drug, which binds to a receptor without activating or inhibiting it but rather prevents other ligands from binding.

Inverse agonism is an important concept in pharmacology and has implications for the development of drugs that target GPCRs and other types of receptors. For example, inverse agonist drugs have been developed to treat certain conditions such as anxiety disorders, where reducing the basal activity of a particular receptor may be beneficial.

The brain is the central organ of the nervous system, responsible for receiving and processing sensory information, regulating vital functions, and controlling behavior, movement, and cognition. It is divided into several distinct regions, each with specific functions:

1. Cerebrum: The largest part of the brain, responsible for higher cognitive functions such as thinking, learning, memory, language, and perception. It is divided into two hemispheres, each controlling the opposite side of the body.
2. Cerebellum: Located at the back of the brain, it is responsible for coordinating muscle movements, maintaining balance, and fine-tuning motor skills.
3. Brainstem: Connects the cerebrum and cerebellum to the spinal cord, controlling vital functions such as breathing, heart rate, and blood pressure. It also serves as a relay center for sensory information and motor commands between the brain and the rest of the body.
4. Diencephalon: A region that includes the thalamus (a major sensory relay station) and hypothalamus (regulates hormones, temperature, hunger, thirst, and sleep).
5. Limbic system: A group of structures involved in emotional processing, memory formation, and motivation, including the hippocampus, amygdala, and cingulate gyrus.

The brain is composed of billions of interconnected neurons that communicate through electrical and chemical signals. It is protected by the skull and surrounded by three layers of membranes called meninges, as well as cerebrospinal fluid that provides cushioning and nutrients.

Adrenergic alpha-2 receptor agonists are a class of medications that bind to and activate adrenergic alpha-2 receptors, which are found in the nervous system and other tissues. These receptors play a role in regulating various bodily functions, including blood pressure, heart rate, and release of certain hormones.

When adrenergic alpha-2 receptor agonists bind to these receptors, they can cause a variety of effects, such as:

* Vasoconstriction (narrowing of blood vessels), which can increase blood pressure
* Decreased heart rate and force of heart contractions
* Suppression of the release of norepinephrine (a hormone and neurotransmitter involved in the "fight or flight" response) from nerve endings
* Analgesia (pain relief)

Adrenergic alpha-2 receptor agonists are used in a variety of medical conditions, including:

* High blood pressure
* Glaucoma (to reduce pressure in the eye)
* Anesthesia (to help prevent excessive bleeding and to provide sedation)
* Opioid withdrawal symptoms (to help manage symptoms such as anxiety, agitation, and muscle aches)

Examples of adrenergic alpha-2 receptor agonists include clonidine, brimonidine, and dexmedetomidine.

Purinergic P2 receptor agonists are substances that bind and activate purinergic P2 receptors, which are a type of cell surface receptor found in many tissues throughout the body. These receptors are activated by extracellular nucleotides, such as ATP (adenosine triphosphate) and ADP (adenosine diphosphate), and play important roles in various physiological processes, including neurotransmission, muscle contraction, and inflammation.

P2 receptors are divided into two main subfamilies: P2X and P2Y. P2X receptors are ligand-gated ion channels that allow the flow of ions across the cell membrane when activated, while P2Y receptors are G protein-coupled receptors that activate intracellular signaling pathways.

Purinergic P2 receptor agonists can be synthetic or naturally occurring compounds that selectively bind to and activate specific subtypes of P2 receptors. They have potential therapeutic applications in various medical conditions, such as pain management, cardiovascular diseases, and neurological disorders. However, their use must be carefully monitored due to the potential for adverse effects, including desensitization of receptors and activation of unwanted signaling pathways.

Carbamates are a group of organic compounds that contain the carbamate functional group, which is a carbon atom double-bonded to oxygen and single-bonded to a nitrogen atom (> N-C=O). In the context of pharmaceuticals and agriculture, carbamates are a class of drugs and pesticides that have carbamate as their core structure.

Carbamate insecticides work by inhibiting the enzyme acetylcholinesterase, which is responsible for breaking down the neurotransmitter acetylcholine in the synapses of the nervous system. When this enzyme is inhibited, acetylcholine accumulates in the synaptic cleft, leading to overstimulation of the nervous system and ultimately causing paralysis and death in insects.

Carbamate drugs are used for a variety of medical indications, including as anticonvulsants, muscle relaxants, and psychotropic medications. They work by modulating various neurotransmitter systems in the brain, such as GABA, glutamate, and dopamine. Carbamates can also be used as anti- parasitic agents, such as ivermectin, which is effective against a range of parasites including nematodes, arthropods, and some protozoa.

It's important to note that carbamate pesticides can be toxic to non-target organisms, including humans, if not used properly. Therefore, it's essential to follow all safety guidelines when handling or using these products.

The hippocampus is a complex, curved formation in the brain that resembles a seahorse (hence its name, from the Greek word "hippos" meaning horse and "kampos" meaning sea monster). It's part of the limbic system and plays crucial roles in the formation of memories, particularly long-term ones.

This region is involved in spatial navigation and cognitive maps, allowing us to recognize locations and remember how to get to them. Additionally, it's one of the first areas affected by Alzheimer's disease, which often results in memory loss as an early symptom.

Anatomically, it consists of two main parts: the Ammon's horn (or cornu ammonis) and the dentate gyrus. These structures are made up of distinct types of neurons that contribute to different aspects of learning and memory.

Ethanolamines are a class of organic compounds that contain an amino group (-NH2) and a hydroxyl group (-OH) attached to a carbon atom. They are derivatives of ammonia (NH3) in which one or two hydrogen atoms have been replaced by a ethanol group (-CH2CH2OH).

The most common ethanolamines are:

* Monethanolamine (MEA), also called 2-aminoethanol, with the formula HOCH2CH2NH2.
* Diethanolamine (DEA), also called 2,2'-iminobisethanol, with the formula HOCH2CH2NHCH2CH2OH.
* Triethanolamine (TEA), also called 2,2',2''-nitrilotrisethanol, with the formula N(CH2CH2OH)3.

Ethanolamines are used in a wide range of industrial and consumer products, including as solvents, emulsifiers, detergents, pharmaceuticals, and personal care products. They also have applications as intermediates in the synthesis of other chemicals. In the body, ethanolamines play important roles in various biological processes, such as neurotransmission and cell signaling.

Cricetinae is a subfamily of rodents that includes hamsters, gerbils, and relatives. These small mammals are characterized by having short limbs, compact bodies, and cheek pouches for storing food. They are native to various parts of the world, particularly in Europe, Asia, and Africa. Some species are popular pets due to their small size, easy care, and friendly nature. In a medical context, understanding the biology and behavior of Cricetinae species can be important for individuals who keep them as pets or for researchers studying their physiology.

Transient receptor potential vanilloid (TRPV) cation channels are a subfamily of transient receptor potential (TRP) channels, which are non-selective cation channels that play important roles in various physiological processes such as nociception, thermosensation, and mechanosensation. TRPV channels are activated by a variety of stimuli including temperature, chemical ligands, and mechanical forces.

TRPV channels are composed of six transmembrane domains with intracellular N- and C-termini. The TRPV subfamily includes six members: TRPV1 to TRPV6. Among them, TRPV1 is also known as the vanilloid receptor 1 (VR1) and is activated by capsaicin, the active component of hot chili peppers, as well as noxious heat. TRPV2 is activated by noxious heat and mechanical stimuli, while TRPV3 and TRPV4 are activated by warm temperatures and various chemical ligands. TRPV5 and TRPV6 are primarily involved in calcium transport and are activated by low pH and divalent cations.

TRPV channels play important roles in pain sensation, neurogenic inflammation, and temperature perception. Dysfunction of these channels has been implicated in various pathological conditions such as chronic pain, inflammatory diseases, and cancer. Therefore, TRPV channels are considered promising targets for the development of novel therapeutics for these conditions.

Opioid receptors are a type of G protein-coupled receptor (GPCR) found in the cell membranes of certain neurons in the central and peripheral nervous system. They bind to opioids, which are chemicals that can block pain signals and produce a sense of well-being. There are four main types of opioid receptors: mu, delta, kappa, and nociceptin. These receptors play a role in the regulation of pain, reward, addiction, and other physiological functions. Activation of opioid receptors can lead to both therapeutic effects (such as pain relief) and adverse effects (such as respiratory depression and constipation).

Cyclic adenosine monophosphate (cAMP) is a key secondary messenger in many biological processes, including the regulation of metabolism, gene expression, and cellular excitability. It is synthesized from adenosine triphosphate (ATP) by the enzyme adenylyl cyclase and is degraded by the enzyme phosphodiesterase.

In the body, cAMP plays a crucial role in mediating the effects of hormones and neurotransmitters on target cells. For example, when a hormone binds to its receptor on the surface of a cell, it can activate a G protein, which in turn activates adenylyl cyclase to produce cAMP. The increased levels of cAMP then activate various effector proteins, such as protein kinases, which go on to regulate various cellular processes.

Overall, the regulation of cAMP levels is critical for maintaining proper cellular function and homeostasis, and abnormalities in cAMP signaling have been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Benzodioxoles are chemical compounds that consist of a benzene ring (a six-carbon cyclic structure with alternating double bonds) linked to two oxide groups through methane bridges. They can be found naturally in some plants, such as nutmeg and tea, but they are also synthesized for use in various pharmaceuticals and illicit drugs.

In the medical field, benzodioxoles are used in the synthesis of certain drugs, including some antimicrobials, antihelmintics (drugs that treat parasitic worm infections), and muscle relaxants. However, they are perhaps best known for their use as a structural component in certain illicit drugs, such as ecstasy (MDMA) and related substances.

It's important to note that while benzodioxoles themselves may have some medical uses, many of the drugs that contain this structure can be dangerous when used improperly or without medical supervision.

Dopamine D2 receptor is a type of metabotropic G protein-coupled receptor that binds to the neurotransmitter dopamine. It is one of five subtypes of dopamine receptors (D1-D5) and is encoded by the gene DRD2. The activation of D2 receptors leads to a decrease in the activity of adenylyl cyclase, which results in reduced levels of cAMP and modulation of ion channels.

D2 receptors are widely distributed throughout the central nervous system (CNS) and play important roles in various physiological functions, including motor control, reward processing, emotion regulation, and cognition. They are also involved in several neurological and psychiatric disorders, such as Parkinson's disease, schizophrenia, drug addiction, and Tourette syndrome.

D2 receptors have two main subtypes: D2 short (D2S) and D2 long (D2L). The D2S subtype is primarily located in the presynaptic terminals and functions as an autoreceptor that regulates dopamine release, while the D2L subtype is mainly found in the postsynaptic neurons and modulates intracellular signaling pathways.

Antipsychotic drugs, which are used to treat schizophrenia and other psychiatric disorders, work by blocking D2 receptors. However, excessive blockade of these receptors can lead to side effects such as extrapyramidal symptoms (EPS), tardive dyskinesia, and hyperprolactinemia. Therefore, the development of drugs that selectively target specific subtypes of dopamine receptors is an active area of research in the field of neuropsychopharmacology.

Capsaicin is defined in medical terms as the active component of chili peppers (genus Capsicum) that produces a burning sensation when it comes into contact with mucous membranes or skin. It is a potent irritant and is used topically as a counterirritant in some creams and patches to relieve pain. Capsaicin works by depleting substance P, a neurotransmitter that relays pain signals to the brain, from nerve endings.

Here is the medical definition of capsaicin from the Merriam-Webster's Medical Dictionary:

caпсаісіn : an alkaloid (C18H27NO3) that is the active principle of red peppers and is used in topical preparations as a counterirritant and analgesic.

Resorcinols are a type of chemical compound that contain a resorcinol moiety, which is made up of a benzene ring with two hydroxyl groups in the ortho position. In medicine, resorcinol and its derivatives have been used for various purposes, including as antiseptics, antibacterials, and intermediates in the synthesis of other pharmaceuticals.

Resorcinol itself has some medicinal properties, such as being able to reduce pain and inflammation, and it has been used topically to treat conditions like eczema, psoriasis, and acne. However, resorcinol can also be toxic in large amounts, so it must be used with caution.

It's important to note that while resorcinol is a chemical compound, the term "resorcinols" may also refer to a group of related compounds that contain the resorcinol moiety. These compounds can have different medicinal properties and uses depending on their specific structure and function.

"Competitive binding" is a term used in pharmacology and biochemistry to describe the behavior of two or more molecules (ligands) competing for the same binding site on a target protein or receptor. In this context, "binding" refers to the physical interaction between a ligand and its target.

When a ligand binds to a receptor, it can alter the receptor's function, either activating or inhibiting it. If multiple ligands compete for the same binding site, they will compete to bind to the receptor. The ability of each ligand to bind to the receptor is influenced by its affinity for the receptor, which is a measure of how strongly and specifically the ligand binds to the receptor.

In competitive binding, if one ligand is present in high concentrations, it can prevent other ligands with lower affinity from binding to the receptor. This is because the higher-affinity ligand will have a greater probability of occupying the binding site and blocking access to the other ligands. The competition between ligands can be described mathematically using equations such as the Langmuir isotherm, which describes the relationship between the concentration of ligand and the fraction of receptors that are occupied by the ligand.

Competitive binding is an important concept in drug development, as it can be used to predict how different drugs will interact with their targets and how they may affect each other's activity. By understanding the competitive binding properties of a drug, researchers can optimize its dosage and delivery to maximize its therapeutic effect while minimizing unwanted side effects.

Pertussis toxin is an exotoxin produced by the bacterium Bordetella pertussis, which is responsible for causing whooping cough in humans. This toxin has several effects on the host organism, including:

1. Adenylyl cyclase activation: Pertussis toxin enters the host cell and modifies a specific G protein (Gαi), leading to the continuous activation of adenylyl cyclase. This results in increased levels of intracellular cAMP, which disrupts various cellular processes.
2. Inhibition of immune response: Pertussis toxin impairs the host's immune response by inhibiting the migration and function of immune cells like neutrophils and macrophages. It also interferes with antigen presentation and T-cell activation, making it difficult for the body to clear the infection.
3. Increased inflammation: The continuous activation of adenylyl cyclase by pertussis toxin leads to increased production of proinflammatory cytokines, contributing to the severe coughing fits and other symptoms associated with whooping cough.

Pertussis toxin is an essential virulence factor for Bordetella pertussis, and its effects contribute significantly to the pathogenesis of whooping cough. Vaccination against pertussis includes inactivated or genetically detoxified forms of pertussis toxin, which provide immunity without causing disease symptoms.

G-protein-coupled receptors (GPCRs) are a family of membrane receptors that play an essential role in cellular signaling and communication. These receptors possess seven transmembrane domains, forming a structure that spans the lipid bilayer of the cell membrane. They are called "G-protein-coupled" because they interact with heterotrimeric G proteins upon activation, which in turn modulate various downstream signaling pathways.

When an extracellular ligand binds to a GPCR, it causes a conformational change in the receptor's structure, leading to the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) on the associated G protein's α subunit. This exchange triggers the dissociation of the G protein into its α and βγ subunits, which then interact with various effector proteins to elicit cellular responses.

There are four main families of GPCRs, classified based on their sequence similarities and downstream signaling pathways:

1. Gq-coupled receptors: These receptors activate phospholipase C (PLC), which leads to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 induces calcium release from intracellular stores, while DAG activates protein kinase C (PKC).
2. Gs-coupled receptors: These receptors activate adenylyl cyclase, which increases the production of cyclic adenosine monophosphate (cAMP) and subsequently activates protein kinase A (PKA).
3. Gi/o-coupled receptors: These receptors inhibit adenylyl cyclase, reducing cAMP levels and modulating PKA activity. Additionally, they can activate ion channels or regulate other signaling pathways through the βγ subunits.
4. G12/13-coupled receptors: These receptors primarily activate RhoGEFs, which in turn activate RhoA and modulate cytoskeletal organization and cellular motility.

GPCRs are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and sensory perception. Dysregulation of GPCR function has been implicated in numerous diseases, making them attractive targets for drug development.

Adenosine A3 receptor agonists are a type of pharmaceutical compound that bind to and activate the adenosine A3 receptor, which is a type of G-protein coupled receptor found in various tissues throughout the body. Activation of the A3 receptor has been shown to have anti-inflammatory and analgesic effects, making it a target for the development of drugs to treat conditions such as rheumatoid arthritis, inflammatory bowel disease, and chronic pain. Examples of adenosine A3 receptor agonists include IB-MECA, Cl-IB-MECA, and MRS1523.

Excitatory amino acid agonists are substances that bind to and activate excitatory amino acid receptors, leading to an increase in the excitation or activation of neurons. The most common excitatory amino acids in the central nervous system are glutamate and aspartate.

Agonists of excitatory amino acid receptors can be divided into two main categories: ionotropic and metabotropic. Ionotropic receptors, such as N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainite receptors, are ligand-gated ion channels that directly mediate fast excitatory synaptic transmission. Metabotropic receptors, on the other hand, are G protein-coupled receptors that modulate synaptic activity through second messenger systems.

Excitatory amino acid agonists have been implicated in various physiological and pathophysiological processes, including learning and memory, neurodevelopment, and neurodegenerative disorders such as stroke, epilepsy, and Alzheimer's disease. They are also used in research to study the functions of excitatory amino acid receptors and their roles in neuronal signaling. However, due to their potential neurotoxic effects, the therapeutic use of excitatory amino acid agonists is limited.

Gamma-Aminobutyric Acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system. It plays a crucial role in regulating neuronal excitability and preventing excessive neuronal firing, which helps to maintain neural homeostasis and reduce the risk of seizures. GABA functions by binding to specific receptors (GABA-A, GABA-B, and GABA-C) on the postsynaptic membrane, leading to hyperpolarization of the neuronal membrane and reduced neurotransmitter release from presynaptic terminals.

In addition to its role in the central nervous system, GABA has also been identified as a neurotransmitter in the peripheral nervous system, where it is involved in regulating various physiological processes such as muscle relaxation, hormone secretion, and immune function.

GABA can be synthesized in neurons from glutamate, an excitatory neurotransmitter, through the action of the enzyme glutamic acid decarboxylase (GAD). Once synthesized, GABA is stored in synaptic vesicles and released into the synapse upon neuronal activation. After release, GABA can be taken up by surrounding glial cells or degraded by the enzyme GABA transaminase (GABA-T) into succinic semialdehyde, which is further metabolized to form succinate and enter the Krebs cycle for energy production.

Dysregulation of GABAergic neurotransmission has been implicated in various neurological and psychiatric disorders, including epilepsy, anxiety, depression, and sleep disturbances. Therefore, modulating GABAergic signaling through pharmacological interventions or other therapeutic approaches may offer potential benefits for the treatment of these conditions.

Muscarinic agonists are a type of medication that binds to and activates muscarinic acetylcholine receptors, which are found in various organ systems throughout the body. These receptors are activated naturally by the neurotransmitter acetylcholine, and when muscarinic agonists bind to them, they mimic the effects of acetylcholine.

Muscarinic agonists can have a range of effects on different organ systems, depending on which receptors they activate. For example, they may cause bronchodilation (opening up of the airways) in the respiratory system, decreased heart rate and blood pressure in the cardiovascular system, increased glandular secretions in the gastrointestinal and salivary systems, and relaxation of smooth muscle in the urinary and reproductive systems.

Some examples of muscarinic agonists include pilocarpine, which is used to treat dry mouth and glaucoma, and bethanechol, which is used to treat urinary retention. It's important to note that muscarinic agonists can also have side effects, such as sweating, nausea, vomiting, and diarrhea, due to their activation of receptors in various organ systems.

Hallucinogens are a class of psychoactive substances that alter perception, mood, and thought, often causing hallucinations, which are profound distortions in a person's perceptions of reality. These substances work by disrupting the normal functioning of the brain, particularly the parts that regulate mood, sensory perception, sleep, hunger, and sexual behavior.

Hallucinogens can be found in various forms, including plants, mushrooms, and synthetic compounds. Some common examples of hallucinogens include LSD (d-lysergic acid diethylamide), psilocybin (found in certain species of mushrooms), DMT (dimethyltryptamine), and ayahuasca (a plant-based brew from South America).

The effects of hallucinogens can vary widely depending on the specific substance, the dose, the individual's personality, mood, and expectations, and the environment in which the drug is taken. These effects can range from pleasant sensory experiences and heightened emotional awareness to terrifying hallucinations and overwhelming feelings of anxiety or despair.

It's important to note that hallucinogens can be dangerous, particularly when taken in high doses or in combination with other substances. They can also cause long-term psychological distress and may trigger underlying mental health conditions. As such, they should only be used under the guidance of a trained medical professional for therapeutic purposes.

Histamine agonists are substances that bind to and activate histamine receptors, leading to the initiation or enhancement of various physiological responses. Histamine is a naturally occurring molecule that plays a key role in the body's immune and allergic responses, as well as in the regulation of sleep, wakefulness, and appetite.

There are four main types of histamine receptors (H1, H2, H3, and H4), each with distinct functions and signaling pathways. Histamine agonists can be selective for one or more of these receptor subtypes, depending on their pharmacological properties.

For example, H1 agonists are commonly used as decongestants and antihistamines to treat allergies, while H2 agonists are used to treat gastroesophageal reflux disease (GERD) and peptic ulcers. H3 agonists have been investigated for their potential therapeutic use in the treatment of neurological disorders such as Parkinson's disease and schizophrenia, while H4 agonists are being studied for their role in inflammation and immune regulation.

It is important to note that histamine agonists can also have adverse effects, particularly if they are not selective for a specific receptor subtype or if they are used at high doses. These effects may include increased heart rate, blood pressure, and bronchodilation (opening of the airways), as well as gastrointestinal symptoms such as nausea, vomiting, and diarrhea.

ICR (Institute of Cancer Research) is a strain of albino Swiss mice that are widely used in scientific research. They are an outbred strain, which means that they have been bred to maintain maximum genetic heterogeneity. However, it is also possible to find inbred strains of ICR mice, which are genetically identical individuals produced by many generations of brother-sister mating.

Inbred ICR mice are a specific type of ICR mouse that has been inbred for at least 20 generations. This means that they have a high degree of genetic uniformity and are essentially genetically identical to one another. Inbred strains of mice are often used in research because their genetic consistency makes them more reliable models for studying biological phenomena and testing new therapies or treatments.

It is important to note that while inbred ICR mice may be useful for certain types of research, they do not necessarily represent the genetic diversity found in human populations. Therefore, it is important to consider the limitations of using any animal model when interpreting research findings and applying them to human health.

"Motor activity" is a general term used in the field of medicine and neuroscience to refer to any kind of physical movement or action that is generated by the body's motor system. The motor system includes the brain, spinal cord, nerves, and muscles that work together to produce movements such as walking, talking, reaching for an object, or even subtle actions like moving your eyes.

Motor activity can be voluntary, meaning it is initiated intentionally by the individual, or involuntary, meaning it is triggered automatically by the nervous system without conscious control. Examples of voluntary motor activity include deliberately lifting your arm or kicking a ball, while examples of involuntary motor activity include heartbeat, digestion, and reflex actions like jerking your hand away from a hot stove.

Abnormalities in motor activity can be a sign of neurological or muscular disorders, such as Parkinson's disease, cerebral palsy, or multiple sclerosis. Assessment of motor activity is often used in the diagnosis and treatment of these conditions.

Drug tolerance is a medical concept that refers to the decreased response to a drug following its repeated use, requiring higher doses to achieve the same effect. This occurs because the body adapts to the presence of the drug, leading to changes in the function or expression of targets that the drug acts upon, such as receptors or enzymes. Tolerance can develop to various types of drugs, including opioids, benzodiazepines, and alcohol, and it is often associated with physical dependence and addiction. It's important to note that tolerance is different from resistance, which refers to the ability of a pathogen to survive or grow in the presence of a drug, such as antibiotics.

Adenosine is a purine nucleoside that is composed of a sugar (ribose) and the base adenine. It plays several important roles in the body, including serving as a precursor for the synthesis of other molecules such as ATP, NAD+, and RNA.

In the medical context, adenosine is perhaps best known for its use as a pharmaceutical agent to treat certain cardiac arrhythmias. When administered intravenously, it can help restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT) by slowing conduction through the atrioventricular node and interrupting the reentry circuit responsible for the arrhythmia.

Adenosine can also be used as a diagnostic tool to help differentiate between narrow-complex tachycardias of supraventricular origin and those that originate from below the ventricles (such as ventricular tachycardia). This is because adenosine will typically terminate PSVT but not affect the rhythm of VT.

It's worth noting that adenosine has a very short half-life, lasting only a few seconds in the bloodstream. This means that its effects are rapidly reversible and generally well-tolerated, although some patients may experience transient symptoms such as flushing, chest pain, or shortness of breath.

Hyperalgesia is a medical term that describes an increased sensitivity to pain. It occurs when the nervous system, specifically the nociceptors (pain receptors), become excessively sensitive to stimuli. This means that a person experiences pain from a stimulus that normally wouldn't cause pain or experiences pain that is more intense than usual. Hyperalgesia can be a result of various conditions such as nerve damage, inflammation, or certain medications. It's an important symptom to monitor in patients with chronic pain conditions, as it may indicate the development of tolerance or addiction to pain medication.

Cyclohexanes are organic compounds that consist of a six-carbon ring arranged in a cyclic structure, with each carbon atom joined to two other carbon atoms by single bonds. This gives the molecule a shape that resembles a hexagonal ring. The carbons in the ring can be saturated, meaning that they are bonded to hydrogen atoms, or they can contain double bonds between some of the carbon atoms.

Cyclohexanes are important intermediates in the production of many industrial and consumer products, including plastics, fibers, dyes, and pharmaceuticals. They are also used as solvents and starting materials for the synthesis of other organic compounds.

One of the most well-known properties of cyclohexane is its ability to exist in two different conformations: a "chair" conformation and a "boat" conformation. In the chair conformation, the carbon atoms are arranged in such a way that they form a puckered ring, with each carbon atom bonded to two other carbons and two hydrogens. This conformation is more stable than the boat conformation, in which the carbon atoms form a flattened, saddle-shaped ring.

Cyclohexanes are relatively nonpolar and have low water solubility, making them useful as solvents for nonpolar substances. They also have a relatively high boiling point compared to other hydrocarbons of similar molecular weight, due to the fact that they can form weak intermolecular forces called London dispersion forces.

Cyclohexane is a flammable liquid with a mild, sweet odor. It is classified as a hazardous substance and should be handled with care. Exposure to cyclohexane can cause irritation of the eyes, skin, and respiratory tract, and prolonged exposure can lead to more serious health effects, including neurological damage.

Patch-clamp techniques are a group of electrophysiological methods used to study ion channels and other electrical properties of cells. These techniques were developed by Erwin Neher and Bert Sakmann, who were awarded the Nobel Prize in Physiology or Medicine in 1991 for their work. The basic principle of patch-clamp techniques involves creating a high resistance seal between a glass micropipette and the cell membrane, allowing for the measurement of current flowing through individual ion channels or groups of channels.

There are several different configurations of patch-clamp techniques, including:

1. Cell-attached configuration: In this configuration, the micropipette is attached to the outer surface of the cell membrane, and the current flowing across a single ion channel can be measured. This configuration allows for the study of the properties of individual channels in their native environment.
2. Whole-cell configuration: Here, the micropipette breaks through the cell membrane, creating a low resistance electrical connection between the pipette and the inside of the cell. This configuration allows for the measurement of the total current flowing across all ion channels in the cell membrane.
3. Inside-out configuration: In this configuration, the micropipette is pulled away from the cell after establishing a seal, resulting in the exposure of the inner surface of the cell membrane to the solution in the pipette. This configuration allows for the study of the properties of ion channels in isolation from other cellular components.
4. Outside-out configuration: Here, the micropipette is pulled away from the cell after establishing a seal, resulting in the exposure of the outer surface of the cell membrane to the solution in the pipette. This configuration allows for the study of the properties of ion channels in their native environment, but with the ability to control the composition of the extracellular solution.

Patch-clamp techniques have been instrumental in advancing our understanding of ion channel function and have contributed to numerous breakthroughs in neuroscience, pharmacology, and physiology.

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WIN 55,212-2 WIN 55,225 Howlett AC, Berglund B, Melvin LS (October 1995). "Cannabinoid Receptor Agonists and Antagonists". ... It is a tricyclic aryl derivative that acts as a competitive antagonist at the CB2 cannabinoid receptor. Its activity at CB1 ... Cannabinoids, Aminoalkylindoles, WIN compounds, 4-Morpholinyl compounds, Anthracenes, All stub articles, Cannabinoid stubs). ...
"Cannabinoid receptors and their endogenous agonists." Annual Review of Pharmacology and toxicology 38, no. 1 (1998): 179-200. ... "Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2 receptor." European Journal of ... "Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor ... "Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal ...
... effects of synthetic cannabinoid receptor agonists are likely due to their action as full receptor agonists and their greater ... the term synthetic cannabinoid typically refers to a full agonist of CB1 and CB2 cannabinoid receptors. According to the review ... 9-THC are partial agonists of cannabinoid receptors. They are less potent and less toxic than many synthetic cannabinoids. It ... It is a partial agonist of CB1 and CB2 cannabinoid receptors with about half the potency of ∆9-THC in most but not all measures ...
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It binds cannabinoid receptors, acting as an inverse agonist at CB1 receptors. Longer forms of hemopressin containing 2-3 ... December 2007). "Hemopressin is an inverse agonist of CB1 cannabinoid receptors". Proc. Natl. Acad. Sci. U.S.A. 104 (51): 20588 ... September 2009). "Novel endogenous peptide agonists of cannabinoid receptors". FASEB J. 23 (9): 3020-9. doi:10.1096/fj.09- ... is also an agonist at CB1 cannabinoid receptors. Hemopressin is not an endogenous peptide but rather an extraction artefact [ ...
Cannabinoid receptor agonists reduce gut motility in IBS patients. Application of CB2-specific antagonists has found that these ... The cannabinoid receptor 2 (CB2), is a G protein-coupled receptor from the cannabinoid receptor family that in humans is ... Later studies examining the effect of synthetic cannabinoid agonist JWH-015 on CB2 receptors revealed that changes in cAMP ... The receptor was identified among cDNAs based on its similarity in amino-acid sequence to the cannabinoid receptor 1 (CB1) ...
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... inverse agonist was rimonabant, discovered in 1994. The endogenous cannabinoid system includes cannabinoid receptors, their ... "An Aromatic Microdomain at the Cannabinoid CB1 Receptor Constitutes an Agonist/Inverse Agonist Binding Region", Journal of ... cannabinoid receptor 1 (CB1) and 2 (CB2). Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit ... Once cannabinoid receptors had been discovered, it became important to establish whether their agonists occur naturally in the ...
"Synthetic Cannabinoid Receptor Agonists (Spice) as New Recreational Psychoactive Substances.". In Preedy VR (ed.). Handbook of ... Cannabinoids, Designer drugs, Cyclohexanols, Phenols, Pfizer brands, All stub articles, Cannabinoid stubs). ... C9)-CP 47,497 (CP 47,497 dimethylnonyl homologue) is a synthetic cannabinoid, a CP 47,497 homologue. Its systematic name is 2 ...
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... produces effects typical of other cannabinoid receptor agonists in animals. It has a somewhat higher oral ... the Δ8 and Δ9 isomers are both known to be cannabinoid receptor agonists, and Δ8-parahexyl has the code number JWH-124, while ... "Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists". The Journal of ... Presumably, it acts as a CB1 agonist in the same way as THC, but as there has been no research published using parahexyl since ...
It is described as a mixed agonist/antagonist at the cannabinoid receptor CB1, meaning that it acts as an antagonist when co- ... Griffin G, Wray EJ, Martin BR, Abood ME (October 1999). "Cannabinoid agonists and antagonists discriminated by receptor binding ... April 1999). "An investigation into the structural determinants of cannabinoid receptor ligand efficacy". British Journal of ... administered alongside a more potent CB1 agonist, but exhibits weak partial agonist effects when administered by itself. ...
... is a chemical compound which is a cannabinoid receptor agonist. It has analgesic effects and is used in scientific ... Structure-activity relationships defining the ACD-tricyclic cannabinoids: cannabinoid receptor binding and analgesic activity. ... "Cannabinoid agonists and antagonists discriminated by receptor binding in rat cerebellum". British Journal of Pharmacology. 128 ... It is an extremely potent CB1 full agonist with a Ki of 0.21 nM, making it more potent than the commonly used full agonist HU- ...
It is a partial agonist at the cannabinoid receptor CB1, producing a maximal stimulation of 58.3% with a Ki of 8.45nM. Griffin ... "Cannabinoid agonists and antagonists discriminated by receptor binding in rat cerebellum". British Journal of Pharmacology. 128 ... April 1999). "An investigation into the structural determinants of cannabinoid receptor ligand efficacy". British Journal of ... yne-delta8-tetrahydrocannabinol at cannabinoid receptors". British Journal of Pharmacology. 128 (3): 735-43. doi:10.1038/sj.bjp ...
Griffin G, Wray EJ, Martin BR, Abood ME (1999). "Cannabinoid agonists and antagonists discriminated by receptor binding in rat ... Cannabinoids, Benzochromenes, Phenols, Carboxamides, All stub articles, Cannabinoid stubs). ... O-1125 (3-(1,1-dimethylhexyl-6-dimethylcarboxamide)-Δ8-tetrahydrocannabinol) is a research chemical which is a cannabinoid ... It is a potent CB1 full agonist with a Ki of 1.16 nM. ...
... (codenamed MK-0364) is a cannabinoid receptor type 1 (CB1) inverse agonist that was investigated as a potential ... Jun 2007). "Antiobesity efficacy of a novel cannabinoid-1 receptor inverse agonist, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3- ... 2007). "Substituted acyclic sulfonamides as human cannabinoid-1 receptor inverse agonists". Bioorganic & Medicinal Chemistry ... Cannabinoid receptor antagonist Armstrong HE, Galka A, Lin LS, Lanza TJ Jr, Jewell JP, Shah SK, et al. ( ...
It is described as a mixed agonist/antagonist at the cannabinoid receptor CB1, meaning that it acts as an antagonist when co- ... Griffin G, Wray EJ, Martin BR, Abood ME (October 1999). "Cannabinoid agonists and antagonists discriminated by receptor binding ... April 1999). "An investigation into the structural determinants of cannabinoid receptor ligand efficacy". British Journal of ... administered alongside a more potent CB1 agonist, but exhibits weak partial agonist effects when administered by itself. ...
AM cannabinoids, Designer drugs, CB1 receptor agonists, CB2 receptor agonists). ... AM-2201 is a full agonist for cannabinoid receptors. Affinities are: with a Ki of 1.0 nM at CB1 and 2.6 nM at CB2. The 4-methyl ... is a recreational designer drug that acts as a potent but nonselective full agonist for the cannabinoid receptor. It is part of ... "First European case of convulsions related to analytically confirmed use of the synthetic cannabinoid receptor agonist AM-2201 ...
March 2011). "Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists". Bioorganic & ... heterocycle derivatives as agonists of the cannabinoid CB1 receptor.", issued 20 April 2010, assigned to Organon NV US 7763732 ... PTI-1 (SGT-48) is an indole-based synthetic cannabinoid. It is one of few synthetic cannabinoids containing a thiazole group ... Cannabinoids, Designer drugs, Diethylamino compounds, All stub articles, Cannabinoid stubs). ...
It acts as a potent and selective cannabinoid receptor agonist, with high potency at both the CB1 and CB2 receptors, but low ... March 2011). "Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists". Bioorganic & ... April 2012). "Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain". Bioorganic & Medicinal ... heterocyclic derivatives as agonists of the CB1 receptor. Discovery of a clinical candidate". Bioorganic & Medicinal Chemistry ...
Cannabinoid receptor agonists are categorized into four groups based on chemical structure. CBN, as one of the many ... Cannabinol (CBN) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors ... endogenously produced cannabinoid receptor ligands). In the brain, the canonical mechanism of CB1 receptor activation is a form ... Each compound acts as a low affinity partial agonist at CB1 receptors with THC demonstrating 10-13x greater affinity to the CB1 ...
... is a drug that presumably acts as a potent agonist for the cannabinoid receptors. It had never previously been reported in the ... Continuing characterization of synthetic cannabinoid receptor agonists". Neuropharmacology. 134 (Pt A): 73-81. doi:10.1016/j. ... In the United States, all CB1 receptor agonists of the 3-(1-naphthoyl)indole class such as MAM-2201 are Schedule I Controlled ... A later study demonstrated that MAM-2201 bound to and activated human CB1 and CB2 cannabinoid receptors and substituted for THC ...
March 2011). "Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists". Bioorganic & ... heterocycle derivatives as agonists of the cannabinoid CB1 receptor.", issued 20 April 2010, assigned to Organon NV US 7763732 ... PTI-2 (SGT-49) is an indole-based synthetic cannabinoid. It is one of few synthetic cannabinoids containing a thiazole group ... Cannabinoids, Designer drugs, Isopropylamino compounds, Ethers, All stub articles, Cannabinoid stubs). ...
Reggio, Patricia H. (2009). "Toward the design of cannabinoid CB1 receptor inverse agonists and neutral antagonists". Drug ... Cannabinoid receptor antagonist Rimonabant Lange JH, Kruse CG (2008). "Cannabinoid CB1 receptor antagonists in therapeutic and ... Lee HK, Choi EB, Pak CS (2009). "The current status and future perspectives of studies of cannabinoid receptor 1 antagonists as ... Drinabant (INN; AVE-1625) is a drug that acts as a selective CB1 receptor antagonist, which was under investigation varyingly ...
... is an inverse agonist of the cannabinoid CB1 receptor. Originally thought to be selective for the CB1 receptor, ... Rimonabant is an inverse agonist for the cannabinoid receptor CB1 and was first-in-class for clinical development. Rimonabant ... Fong TM, Heymsfield SB (September 2009). "Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action ... CB1 receptor antagonists, Chlorobenzenes, 1-Piperidinyl compounds, Pyrazoles, Withdrawn drugs, Cannabinoids, Mu-opioid receptor ...
... is an indole-based synthetic cannabinoid that is a potent agonist of the CB1 receptor and has been sold online as a ... Meyyappan C, Ford L, Vale A (February 2017). "Poisoning due to MDMB-CHMICA, a synthetic cannabinoid receptor agonist". Clinical ... September 2016). "Clinical toxicity following analytically confirmed use of the synthetic cannabinoid receptor agonist MDMB- ... "Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA" (PDF). ...
Deutsch DG, Chin SA (September 1993). "Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist". ... and their activation of cannabinoid receptors. Activation of the cannabinoid receptor CB1 or CB2 in different tissues, ... a cannabinoid receptor (CB) agonist. Due to the ability of FAAH to regulate nociception, it is currently viewed as an ... And by its cannabinoid receptor activation, the influence of cannabis on insulin observed in an human study, is in line with ...
Pertwee RG (2012). "Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and ... Cannabinoid medication might be useful in the treatment of the symptoms in patients with TS, but the 2009 review found that the ... Cannabinoids have been proposed for the treatment of primary anorexia nervosa, but have no measurable beneficial effect. The ... "Cannabis and Cannabinoids (PDQ®)". National Cancer Institute at the National Institutes of Health. National Cancer Institute. 2 ...
January 2008). "Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI". ... that acts as a selective full agonist of the peripheral cannabinoid receptor CB2, but with much lower affinity for the ... UR-144 has high affinity for the CB2 receptor with a Ki of 1.8 nM but 83x lower affinity for the CB1 receptor with a Ki of 150 ... WO application 2006069196, Pace JM, Tietje K, Dart MJ, Meyer MD, "3-Cycloalkylcarbonyl indoles as cannabinoid receptor ligands ...
The specific CB2 cannabinoid receptor agonist JWH-133 induced cognitive improvement in double AβPP/PS1 transgenic mice, a ... CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice J Alzheimers Dis. 2013;35(4):847-58. doi ... The specific CB2 cannabinoid receptor agonist JWH-133 induced cognitive improvement in double AβPP/PS1 transgenic mice, a ... In conclusion, the present study lends support to the idea that stimulation of CB2 receptors ameliorates several altered ...
... chemical compounds that activate the same receptors as delta-9-tetrahydrocannabinol (THC), the active component of marijuana ( ... Cannabinoid receptor agonists. A cannabidiol oral solution (Epidiolex) was approved by the US Food and Drug Administration (FDA ... Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic ... it shows the biosynthesis of AEA and activation of the cannabinoid binding receptor-1 (CB1-R) receptor pathway (2- ...
Coombs, T, Abdelkader, A, Al-Jumeily, D and Assi, S (2022) Rapid Detection of Synthetic Cannabinoid Receptor Agonists ... Rapid Detection of Synthetic Cannabinoid Receptor Agonists Impregnated into Paper by Raman Spectroscopy ... Synthetic cannabinoid and paper samples were measured non-destructively using a handheld Raman spectrometer equipped with a ... The results showed that Raman spectroscopy could identify specific synthetic cannabinoids in papers that were either deposited ...
WIN 54,461 (6-Bromopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB2 ... "Cannabinoid Receptor Agonists and Antagonists". Current Pharmaceutical Design. 1 (3): 343-352. doi:10.2174/ ... Cannabinoids, Aminoalkylindoles, WIN compounds, Benzoylindoles, 4-Morpholinyl compounds, Organobromides, All stub articles, ...
cannabinoid. receptor. agonists /. neocannabinoids. Classical cannabinoids. (dibenzopyrans). *9-OH-HHC. *9-Nor-9β-HHC ... O-1871 is a potent cannabinoid agonist which was invented by Billy R Martin and Raj K Razdan at Organix Inc in 2002. It has a ... CB1 receptor affinity of 2.0nM and a CB2 receptor affinity of 0.3nM.[1] Structurally, O-1871 is a cyclohexylphenol derivative ... This cannabinoid related article is a stub. You can help Wikipedia by expanding it. ...
Synthetic cannabinoid receptor agonists Structure:. CAS Number: InChI: InChI=1S/C19H26FN3O3/c1-19(2,3)16(18(25)26-4)21-17(24)15 ...
Finding Order in Chemical Chaos - Continuing Characterization of Synthetic Cannabinoid Receptor Agonists NCJ Number ... Surface Enhanced Raman Spectroscopy (SERS) as a Method for the Toxicological Analysis of Synthetic Cannabinoids NCJ Number ... The next generation of synthetic cannabinoids: Detection, activity, and potential toxicity of pent-4en and but-3en analogues ... The next generation of synthetic cannabinoids: Detection, activity, and potential toxicity of pent-4en and but-3en analogues ...
Cannabinoid Cb1 Receptor Agonists Do Not Lower, However May Improve Acoustic Trauma-induced Tinnitus In Pmc Rats. Leave a ... Cannabinoid Cb1 Receptor Agonists Do Not Lower, But Might Increase Acoustic Trauma-induced Tinnitus In Pmc Rats ...
Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; toward Robust ... Cannabis and Cannabinoids, Chemistry, Crime Scene Investigation and Reconstruction, DREs / Traffic Safety Resource Prosecutors ...
Cannabimimetic effects of abused indazole-carboxamide synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA and 5F- ... Cannabimimetic effects of abused indazole-carboxamide synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA and 5F- ...
Synthetic cannabinoid receptor agonists: analytical profiles and development of QMPSB, QMMSB, QMPCB, 2F-QMPSB, QMiPSB, and SGT- ... Drug Testing and Analysis - 2020 - Brandt - Synthetic cannabinoid receptor agonists Analytical profiles and development of.pdf ... Synthetic cannabinoid receptor agonists: analytical profiles and development of QMPSB, QMMSB, QMPCB, 2F-QMPSB, QMiPSB, and SGT- ... have become known as synthetic cannabinoid receptor agonists (SCRAs). One group of SCRAs that has received little attention ...
AM251, a cannabinoid receptor 1 reverse agonist known to facilitate adult neurogenesis and synaptic plasticity, may help to ... The Cannabinoid Receptor 1 Reverse Agonist AM251 Ameliorates Radiation-Induced Cognitive Decrements.. Parihar, Vipan K; Syage, ...
One way to avoid cannabinoid receptor subtype 1 (CB1R)-mediated central side-effects is to develop CB1R agonists with limited ... but the relative contribution of peripheral CB1Rs to the analgesic effects of systemic cannabinoids remains unclear. Here we ... addressed this by exploring the analgesic properties and site of action AZ11713908, a peripherally restricted CB1R agonist, in ... Cannabinoids are analgesic in man, but their use is limited by their psychoactive properties. ...
The effect of cannabinoid receptor agonist WIN 55,212-2 on anxiety-like behavior and locomotion in a genetic model of absence ... The effect of cannabinoid receptor agonist WIN 55,212-2 on anxiety-like behavior and locomotion in a genetic model of absence ... GAERS and NEC rats were treated with cannabinoid 1/2 receptor agonist WIN 55,212-2 2 mg/kg and tested on the Elevated Plus-Maze ...
... cannabinoid 1 receptor; cannabinoid 2 receptor; 2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo1,2,3 de1, ... Previous studies have shown that cannabinoid receptor agonists have analgesic effects in various models of pain. In this study ... Evaluation of protective effects of non-selective cannabinoid receptor agonist WIN 55,212-2 against the nitroglycerine-induced ... Cannabinoid Receptor Agonists; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Male; Migraine Disorders; ...
Seely, K. A. Cannabinoid receptor inverse agonists as novel therapeutic agents." The Sciences and Engineering. The Sciences and ... Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci U S ... Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 2000;141:3657-67. ... Resveratrol acts as an estrogen receptor (ER) agonist in breast cancer cells stably transfected with ER alpha. Int.J.Cancer 5-1 ...
Cannabinoid receptor agonists protect cultured rat hippocampal neurons... Mol Pharmacol. 1998. de Bruin NM, Ellenbroek B.... ... Dexanabinol: A novel cannabinoid with neuroprotective properties IDrugs. 2003. Moyano S, Frechilla D, De.... NMDA receptor ... LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA recepto... Eur J Neurosci. 1999. ... Effects of the 5-HT(2A) Agonist Psilocybin on Mismatch Negativity Gene... Neuropsychopharmacol.... 2002. ...
They demonstrate its capabilities by visualizing cariprazine binding to D3 dopamine receptors on Islands of Calleja granule ... we took advantage of PharmacoSTORM to provide in vivo evidence that cariprazine predominantly binds to D3 dopamine receptors on ... We exploited rational chemical design for fluorophore-tagged high-affinity receptor ligands and an enzyme inhibitor; and ... Crystal structures of agonist-bound human cannabinoid receptor CB 1. Nature 547, 468-471 (2017). ...
... using the synthetic cannabinoid receptor agonist WIN55,212-2 (WIN), in order to assess measures of relapse/reinstatement of ... Therefore, the current study sought to develop a rodent model of adolescent cannabinoid self-administration (SA), ... Thus, SA of a rewarding cannabinoid in adolescence does not produce long-term cognitive dysfunction. ... the synthetic cannabinoid receptor agonist, WIN55,212-2 (WIN), which is a more potent agonist at cannabinoid receptors (CB) 1 ...
TRPV1 and CB1 receptors share the endogenous agonist anandamide (AEA), produced from N-arachidonoylphosphatidylethanolamine (20 ... and cannabinoid receptor 1 (CB1) are essential in the modulation of nociceptive signaling in the spinal cord dorsal horn that ... TRPV1 and CB1 receptors share the endogenous agonist anandamide (AEA), produced from N-arachidonoylphosphatidylethanolamine (20 ... In addition, the inhibition was prevented by the CB1 receptor antagonist PF 514273 (0.2 μM) but not by the TRPV1 receptor ...
GABAB receptors and CB1Rs(Glu) are insensitive to BDNF. A, The depressant effect of the GABAB receptor agonist baclofen on ... 2009) Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and ... or also involved other receptors. Application of the GABAB receptor agonist baclofen (n = 7) significantly (p , 0.01) reduced ... A, The graph shows that the depressant effect of the CB1 receptor agonist HU210 on sIPSC was completely abolished by incubation ...
... is an agonist to both the CB1 and the CB2 subtype of cannabinoid receptors. It is available on prescription in several ... There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptor subtypes and ... is an agonist to both the CB1 and the CB2 subtype of cannabinoid receptors. It is available on prescription in several ... antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also promising candidates for ...
Inverse agonists for the cannabinoid receptor drugs are potential candidates for an efficient pharmacological approach. ... Endocannabinoid receptors, and hypothalamic-pituitary-adrenal axis dysregulation and sympathetic hyperactivation are the most ...
... priming presynaptic cannabinoid 1 receptors for desensitization upon subsequent addition of exogenous agonists. Despite the ... their efficacy may be limited by pain-induced adaptations in the cannabinoid system. Cannabinoid receptor subtype 1 (CB1Rs) ... Endocannabinoids readily induce cannabinoid 1 receptor desensitization if their degradation is blocked, indicating that ... In naïve rats, exogenous cannabinoid agonists robustly reduce both eIPSCs and mIPSCs. After 5-7 days of inflammation, the ...
This review will summarize the data regarding those natural and synthetic cannabinoids that increase pro-inflammatory cytokines ... Cannabis and synthetic cannabinoids in particular gained significant popularity in the past years. There is an increasing ... will further contribute to this yet less explored connection and propose the KP to be the missing link between cannabinoid- ... Potts, A.J.; Cano, C.; Thomas, S.H.L.; Hill, S.L. Synthetic cannabinoid receptor agonists: Classification and nomenclature. ...
view grouping Novel Cannabinoid Receptor Agonists). General. First Times. Combinations. Retrospective / Summary. ...
Differential activation of G proteins by synthetic cannabinoid receptor agonists, utilizing the CAMYEL BRET biosensor. ... Agonist stimulation gave a transient increase in pERK1/2, peaking at 5 min for both Gi and Gq receptor activation. Using the 5 ... G-protein coupled receptors (GPCRs) are a large family of receptors which have a broad involvement in cellular responses ... Synthetic cannabinoids become increasingly associated to drug misuse. Read how the CAMYEL BRET biosensor can be used to study ...
2015). Cannabinoid CB1 receptor agonists do not decrease, but may increase acoustic trauma-induced tinnitus in rats.. https:// ... When endocannabinoids bind to either CB1 or CB2 receptors, this produces effects depending on the location of the receptors. ... CBD is a cannabinoid from the cannabis plant that wont get you "high" like tetrahydrocannabinol (THC) does. There are three ... Both full-spectrum and broad-spectrum CBD contain other cannabinoids, flavonoids, and terpenes from the cannabis plant. Full- ...
Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial ... The aryl hydrocarbon receptor in anticancer drug discovery: friend or foe? Current Pharmaceutical Design. 8(27), 2475-90 ... Aryl hydrocarbon receptor mediates sensitivity of MCF-7 breast cancer cells to antitumor agent 2-(4-amino-3-methylphenyl) ... Update to: the aryl hydrocarbon receptor in anticancer drug discovery: friend or foe? Medicinal Chemistry Reviews - Online. 2(2 ...
  • Humans and animals alike naturally synthesize endocannabinoids, chemical compounds that activate the same receptors as delta-9-tetrahydrocannabinol (THC), the active component of marijuana ( Cannabis sativa ). (medscape.com)
  • Monoacylglycerol lipase protects the presynaptic cannabinoid 1 receptor from desensitization by endocannabinoids after persistent inflammation. (iasp-pain.org)
  • Despite the reduced efficacy of exogenous agonists, endocannabinoids have prolonged efficacy after persistent inflammation. (iasp-pain.org)
  • Endocannabinoids readily induce cannabinoid 1 receptor desensitization if their degradation is blocked, indicating that endocannabinoid concentrations are maintained at sub-desensitizing levels and that degradation is critical for maintaining endocannabinoid regulation of presynaptic GABA release in the ventrolateral periaqueductal gray during inflammatory states. (iasp-pain.org)
  • It also makes molecules called endocannabinoids which are similar to cannabinoids found in the cannabis plant. (healthline.com)
  • When endocannabinoids bind to either CB1 or CB2 receptors, this produces effects depending on the location of the receptors. (healthline.com)
  • For example, endocannabinoids produced by your body might bind to immune cell receptors to let your body know it's experiencing inflammation . (healthline.com)
  • Still, they're aware that CBD binds differently to CB1 and CB2 receptors compared with THC - possibly by preventing the breakdown of endocannabinoids. (healthline.com)
  • The activation of CB1 receptors by endocannabinoids or agonists is said to increase stress resilience and reduce anxiety symptoms. (naturalnews.com)
  • Endocannabinoids are endogenous lipid neurotransmitters that activate cannabinoid receptors and play a role in regulating motivated behaviors, such as feeding, anxiety, drug seeking, pain, and reproduction [ 4 , 5 ]. (hindawi.com)
  • The components of the ECS, including endocannabinoids, their cognate enzymes and cannabinoid receptors, are localized in the eye, and evidence indicates that ECS modulation plays a role in ocular disease states. (frontiersin.org)
  • Several reports have shown modulation of Cys-loop receptors by phytocannabinoids and endocannabinoids independent of cannabinoid receptors with potential physiological or therapeutic consequences. (researchgate.net)
  • The endocannabinoid system comprises at least two G-protein-coupled receptors (the cannabinoid CB1 and CB2 receptors) activated by marijuana's psychoactive principle ∆9-tetrahydrocannabinol (THC) and the endogenous ligands known as endocannabinoids. (benthamscience.com)
  • A diverse assortment of molecules designed to explore the cannabinoid receptor system and considered new psychoactive substances (NPS) have become known as synthetic cannabinoid receptor agonists (SCRAs). (ljmu.ac.uk)
  • Therefore, the current study sought to develop a rodent model of adolescent cannabinoid self-administration (SA), using the synthetic cannabinoid receptor agonist WIN55,212-2 (WIN), in order to assess measures of relapse/reinstatement of drug seeking and long-term effects on cognitive function assessed in a delay-match-to-sample working memory task and a spatial recognition task. (nature.com)
  • Dronabinol (Delta 9-tetrahydocannabinol, THC), the main source of the pharmacological effects caused by the use of cannabis, is an agonist to both the CB1 and the CB2 subtype of cannabinoid receptors. (nih.gov)
  • Cannabinoid-targeted pain therapies are increasing with the expansion of cannabis legalization, however, their efficacy may be limited by pain-induced adaptations in the cannabinoid system. (iasp-pain.org)
  • CBD is a cannabinoid from the cannabis plant that won't get you "high" like tetrahydrocannabinol (THC) does. (healthline.com)
  • Both full-spectrum and broad-spectrum CBD contain other cannabinoids, flavonoids , and terpenes from the cannabis plant. (healthline.com)
  • Med Cannabis Cannabinoids (2019) 1 (2): 112-118. (karger.com)
  • Observational studies have shown that medical cannabis patients in general use cannabinoids as a substitution for alcohol, illicit drugs, and/or commonly used prescription drugs for better symptom management, as well as to experience fewer side effects [ 7, 8 ]. (karger.com)
  • THC's strong affinity with CB1 receptors is the reason why you get high from consuming cannabis. (cfah.org)
  • THCA (Tetrahydrocannabinolic acid) is a non-psychotropic cannabinoid found in living cannabis plants. (cfah.org)
  • The U.S. approval of Epidiolex in June 2018 - the first plant-based cannabinoid to be approved by the FDA - is viewed as a huge shift forward for the science surrounding cannabis, providing a pathway for other cannabinoid-based drugs to come to the market. (pharmavoice.com)
  • Given that CBD is not a CB1 agonist, it is free from psychotomimetic properties and lacks cannabis-like intoxicating effects. (genengnews.com)
  • A class of G-protein-coupled receptors that are specific for CANNABINOIDS such as those derived from CANNABIS. (bvsalud.org)
  • The non-psychotropic cannabidiol (CBD), some analogues of natural cannabinoids and their metabolites, antagonists at the cannabinoid receptors and modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. (nih.gov)
  • Ketamine and Phencyclidine (PCP) Ketamine and phencyclidine are N-methyl-D-aspartate receptor antagonists and dissociative anesthetics that can cause intoxication, sometimes with confusion or a catatonic state. (msdmanuals.com)
  • We've all got an endocannabinoid system (ECS) consisting of endocannabinoid receptors throughout the body. (healthline.com)
  • This paper also briefly discusses the endocannabinoid system in relation to ADHD, although more preclinical and clinical research is warranted to establish the optimal levels of cannabinoids, terpenes, and dosing regimens, which vary between different ADHD patients. (karger.com)
  • THCA doesn't bind well with either of the cannabinoid receptors in the endocannabinoid system (ECS). (cfah.org)
  • This group of G protein-coupled receptors share lipid mediators as ligands. (rndsystems.com)
  • Functional selectivity in CB(2) cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB(2) ligands. (iu.edu)
  • Gallant et al (1996) New class of potent ligands for the human peripheral cannabinoid receptor. (tocris.com)
  • Our Cannabinoid review gives an overview of the pharmacological ligands used to study the cannabinoid CB1 and CB2 receptors. (tocris.com)
  • some of these drugs are more potent and efficacious agonists than THC and have been associated with outbreaks of overdose-related illness in multiple states. (cdc.gov)
  • CP47,497-C8 and JWH073, commonly found in 'Spice' herbal blends, are potent and efficacious CB(1) cannabinoid receptor agonists. (iu.edu)
  • JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. (iu.edu)
  • CBD and 2-AG were positive allosteric modulators at α1-6βγ2 receptors, with low micromolar potencies. (researchgate.net)
  • These adaptations with inflammation have important implications for the development of cannabinoid-based pain therapeutics targeting MAGL and CB1Rs.Presynaptic G protein-coupled receptors are resistant to desensitization. (iasp-pain.org)
  • G-protein coupled receptors (GPCRs) are a large family of receptors which have a broad involvement in cellular responses affecting many important body functions both in health and disease. (bmglabtech.com)
  • Expression of G protein-coupled receptors and related proteins in HEK293, AtT20, BV2, and N18 cell lines as revealed by microarray analysis. (iu.edu)
  • WIN 54,461 (6-Bromopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB2. (wikipedia.org)
  • Injecting proestrus, but not hormone primed, rats with a CB 1 (cannabinoid receptor 1) antagonist/inverse agonist and GPR18 antagonist, AM251 facilitated sexual motivation [ 4 ]. (hindawi.com)
  • morpholinylamide (BML-190), an inverse agonist for the peripheral cannabinoid receptor (CB(2)) in rat liver microsomes. (tocris.com)
  • TRPV1 and CB 1 receptors share the endogenous agonist anandamide (AEA), produced from N-arachidonoylphosphatidylethanolamine (20:4-NAPE). (frontiersin.org)
  • Five endogenous cannabinoids have been detected so far, of whom anandamide and 2-arachidonylglycerol are best characterized. (nih.gov)
  • Anandamide and 2-AG are high-affinity agonists for the GPCR cannabinoid receptors CB 1 and CB 2 . (jci.org)
  • As to CB1, CBD is considered to be a negative allosteric modulator, which means, it modifies this receptor in such a way that the binding of classical agonists such as anandamide (AEA), THC, or nabilone is dramatically reduced. (genengnews.com)
  • GAERS and NEC rats were treated with cannabinoid 1/2 receptor agonist WIN 55,212-2 2 mg/kg and tested on the Elevated Plus-Maze. (cardiff.ac.uk)
  • Cannabinoid receptor subtype 1 (CB1Rs) inhibition of spontaneous, miniature and evoked GABAergic postsynaptic currents (mIPSCs and eIPSCs) in the ventrolateral periaqueductal gray (vlPAG) were compared in slices from naïve and inflamed male and female Sprague-Dawley rats. (iasp-pain.org)
  • In naïve rats, exogenous cannabinoid agonists robustly reduce both eIPSCs and mIPSCs. (iasp-pain.org)
  • The cannabinoid CB 2 receptor agonist GW405833 does not ameliorate brain damage induced by hypoxia-ischemia in rats. (otago.ac.nz)
  • Cannabinoid agonist, WIN 55,212-2 (WIN), administered to male rats reduced intromission frequency and increased intervals between ejaculations [ 4 ]. (hindawi.com)
  • Endogenous cannabinoids (eCBs) are involved in the development and regulation of reproductive behaviors. (hindawi.com)
  • Validating antibodies to the cannabinoid CB2 receptor: Antibody sensitivity is not evidence of antibody specificity. (otago.ac.nz)
  • R&D Systems offers antibodies for the receptors listed below, as well as agonists for the cannabinoid receptors. (rndsystems.com)
  • Additionally, AM251 and AM630 (CB1 and CB2 receptor antagonist, respectively, 1 mg/kg, i.p.) were used to evaluate the possible involvement of CB1 and CB2 receptors during the protective effects of WIN 55,212-2. (ac.ir)
  • In acute model, we found that WIN 55,212-2 (almost high doses) decreases the level of pain mainly through CB1 receptor due to CB1 antagonist abrogates its protective effects, however, in formalin test CB2 receptors also had crucial roles in both phases at 3 mg/kg of WIN 55,212-2. (ac.ir)
  • The N-methyl-D-aspartate (NMDA) receptor antagonist, dextrorphan, prev. (erowid.org)
  • In addition, the inhibition was prevented by the CB 1 receptor antagonist PF 514273 (0.2 μM) but not by the TRPV1 receptor antagonist SB 366791 (10 μM). (frontiersin.org)
  • Under inflammatory conditions, 20:4-NAPE (20 μM) also exhibited a significant inhibitory effect (74.5 ± 8.9%) on the mEPSCs frequency that was prevented by the TRPV1 receptor antagonist SB 366791 but not by PF 514273 application. (frontiersin.org)
  • In mice lacking one copy of the BDNF gene ( BDNF +/− ), CB 1 R (GABA) responses were potentiated and were preserved from the action of haloperidol, a DA D 2 receptor (D 2 R) antagonist able to fully abolish CB 1 R (GABA) function in rewarded animals. (jneurosci.org)
  • Previous studies have shown that cannabinoid receptor agonists have analgesic effects in various models of pain. (ac.ir)
  • Significance: Our data supported the argument that activation of CB1 and CB2 receptors by WIN 55,212-2 may be considered a new medication for migraine, however in lack of each receptor leads to different responses from deletion to the reduction of analgesic effects. (ac.ir)
  • In this regard, CBD inhibition of 5-HT 3 receptors may contribute to its role in modulation of nociception and emesis, potentiation of GABA receptors may account for its anti-seizure, anxiolytic and analgesic effects, and potentiation of glycine receptors may be relevant for CBD anti-nociceptive actions [3,16, 22] . (researchgate.net)
  • Transient receptor potential ion channel, vanilloid subfamily, type 1 (TRPV1) cation channel, and cannabinoid receptor 1 (CB 1 ) are essential in the modulation of nociceptive signaling in the spinal cord dorsal horn that underlies different pathological pain states. (frontiersin.org)
  • There is evidence that besides the two cannabinoid receptor subtypes cloned so far additional cannabinoid receptor subtypes and vanilloid receptors are involved in the complex physiological functions of the cannabinoid system that include motor coordination, memory procession, control of appetite, pain modulation and neuroprotection. (nih.gov)
  • CGRP release was induced by either 60 mM K + (for depolarization-induced stimulation) or 100 nM capsaicin (for transient receptor potential vanilloid 1 (TRPV1) -induced stimulation) and measured using an enzyme-linked immunosorbent assay. (lu.se)
  • Research has largely been restricted to date due to cannabinoids being Schedule I. As more people recognize the therapeutic potential of these molecules, DEA licensed parties such as formulation labs, CDMOs, and academic labs are increasingly interested in participating in innovation. (pharmavoice.com)
  • Background: Based on the current understanding of the role of neuropeptide signalling in migraine, we explored the therapeutic potential of a specific cannabinoid agonist. (lu.se)
  • In this study, therefore, we investigated anti-nociceptive effects of WIN 55,212-2, and the role of either CB1 or CB2 receptors in nitroglycerine (NTG)-induced animal model of migraine. (ac.ir)
  • Both compounds can act synergistically with each other, especially when accompanied by minor cannabinoids and terpenes. (cfah.org)
  • AM251, a cannabinoid receptor 1 reverse agonist known to facilitate adult neurogenesis and synaptic plasticity , may help to ameliorate radiation -induced CNS impairments. (bvsalud.org)
  • CB2 cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons. (iu.edu)
  • Here we used two-electrode voltage clamp electrophysiology to compare the actions of CBD with those of the major central endocannabinoid, 2-arachidonoyl glycerol (2-AG) on human recombinant GABAA receptors (synaptic α1-6βg2 and extrasynaptic α4β2δ) expressed on Xenopus oocytes. (researchgate.net)
  • The Cannabinoid Receptor 1 Reverse Agonist AM251 Ameliorates Radiation-Induced Cognitive Decrements. (bvsalud.org)
  • ERK phosphorylation is demonstrated at receptors which signal via Gi and Gq G-proteins. (bmglabtech.com)
  • Inhibition of GABA release by presynaptic mu opioid receptors (MORs) in the vlPAG does not desensitize with persistent inflammation. (iasp-pain.org)
  • Unexpectedly, while CB1R desensitization significantly reduces inhibition produced by exogenous agonists, depolarization-induced suppression of inhibition (DSI) protocols that promote 2-AG synthesis exhibit CB1R activation after inflammation. (iasp-pain.org)
  • The aim of the present study was to examine the effect of the synthetic endocannabinoid (eCB) analogue, arachidonyl-2′-chloroethylamide (ACEA), on calcitonin gene-related peptide (CGRP) release in the dura and trigeminal ganglion (TG), as cannabinoids are known to activate G i/o -coupled cannabinoid receptors type 1 (CB1), resulting in neuronal inhibition. (lu.se)
  • coupled cannabinoid receptors type 1 (CB1), resulting in neuronal inhibition. (lu.se)
  • When treated with WIN55,212-2 (non-selective), ACEA (CBr1-selective) or AM1241 (CBr2-selective) agonists in vitro, oral cancer cell proliferation was significantly attenuated in a dose-dependent manner. (420magazine.com)
  • Dexmedetomidine is a highly-selective alpha-2a receptor agonist and we haven't really had one of those before in psychiatry for this purpose. (medscape.com)
  • To date, there has been limited use of translational models for understanding cannabinoid abuse liability, mechanisms of addiction, or effects of self-administered dosing patterns on cognition. (nature.com)
  • Zawilska and Wojcieszak, 2014 ), but use of WIN can clarify the effects of cannabinoid receptor agonist SA on behavior. (nature.com)
  • After 5-7 days of inflammation, the effects of exogenous cannabinoids are significantly reduced due to CB1R desensitization via GRK2/3, as function is recovered in the presence of the GRK2/3 inhibitor, Compound 101 (Cmp101). (iasp-pain.org)
  • After experiencing adverse effects from prolonged use of this medication and afterwards other medications that were prescribed as alternatives, the patient discovered that cannabinoid therapeutics (CT) had been experimented inside the EU area to treat patients with ADHD. (karger.com)
  • He was treated with standardized cannabinoids in botanical (whole-plant) form between 2010 and 2016, after experiencing adverse effects from immediate-release methylphenidate. (karger.com)
  • These effects can be more energizing or sedating depending on the terpene content of a specific strain and the ratios between THC and other cannabinoids. (cfah.org)
  • These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation. (unige.ch)
  • Novel studies investigating cannabinoids and obstructive sleep apnea suggest that synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas. (springer.com)
  • Gafner believes these alkamides potentially exert their anxiolytic effects by binding to cannabinoid 1 (CB1) receptors in the brain. (naturalnews.com)
  • The ocular effects of cannabinoids have been studied extensively in animals and humans over the last few decades. (frontiersin.org)
  • It was not until the 1990's, however, that the effects of cannabinoids in the eye were formally ascribed to actions on the ocular ECS (reviewed in Yazulla, 2008 ). (frontiersin.org)
  • The ocular hypotensive effects of cannabinoids, specifically, have generated considerable interest over the last few decades largely due to their potential use in the treatment of glaucoma. (frontiersin.org)
  • Despite evidence that some endogenous and synthetic cannabinoids interact with GABAA receptors, no-one has yet investigated the effects of CBD. (researchgate.net)
  • The potency of CBD increased and efficacy preserved in binary α1/α2β2 receptors indicating that their effects do not involve the classic benzodiazepine site. (researchgate.net)
  • Taken together these results reveal a mode of action of CBD on specifically configured GABAA receptors that may be relevant to the anticonvulsant and anxiolytic effects of the compound. (researchgate.net)
  • CBD shows insufficient binding to the cannabinoid receptors, particularly to CB1, which is involved in psychotomimetic effects. (genengnews.com)
  • We investigated the effects of cannabinoid receptor agonists on (1) oral cancer cell viability in vitro and (2) oral cancer pain and tumor growth in a mouse cancer model. (420magazine.com)
  • At the conclusion of today's session the participant will be able to describe the epidemiology and clinical effects of synthetic cannabinoid use, discuss recent clusters of severe disease associated with synthetic cannabinoid use in the US, identify opportunities for clinicians to support surveillance and response efforts. (cdc.gov)
  • Comment: Naltrexone may enhance therapeutic effects of cannabinoids. (medscape.com)
  • One of the classes of new psychoactive substances that have been commonly concealed in papers and that have been linked to toxicity and hospitalization cases is synthetic cannabinoids. (ljmu.ac.uk)
  • Cannabinoids, Synthetic Synthetic cannabinoids are manufactured drugs that are tetrahydrocannabinol (THC) receptor agonists. (msdmanuals.com)
  • LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA recepto. (erowid.org)
  • The maximal level of enhancement seen with either CBD or 2-AG were on α2-containing GABAA receptor subtypes, with approximately a 4-fold enhancement of the GABA EC5 evoked current, more than twice the potentiation seen with other α-subunit receptor combinations. (researchgate.net)
  • Our results show that 20:4-NAPE application has a significant modulatory effect on spinal cord nociceptive signaling that is mediated by both TRPV1 and CB 1 presynaptic receptors, whereas peripheral inflammation changes the underlying mechanism. (frontiersin.org)
  • Here we find that persistent inflammation increases endocannabinoid levels, priming presynaptic cannabinoid 1 receptors for desensitization upon subsequent addition of exogenous agonists. (iasp-pain.org)
  • Synapse-specific expression of mu opioid receptor long-term depression in the dorsomedial striatum. (iu.edu)
  • Alcohol exposure disrupts mu opioid receptor-mediated long-term depression at insular cortex inputs to dorsolateral striatum. (iu.edu)
  • Potential for additive opioid receptor anatagonism and increased risk of opioid withdrawal. (medscape.com)
  • Exploration of extrasynaptic α4β2δ receptors revealed that both compounds enhanced GABA EC5 evoked currents at concentrations ranging from 0.01-1 μM. (researchgate.net)
  • The receptor class may play a role in modulating the release of signaling molecules such as NEUROTRANSMITTERS and CYTOKINES. (bvsalud.org)
  • NeuroTherapia is developing an orally available cannabinoid receptor agonist, NTRX-07, for the treatment of neuroinflammation, which likely plays a critical role in the progression of neurodegenerative diseases. (prnewswire.com)
  • NTRX-07 is a small orally-available molecule that targets receptors that are known to be increased in diseases including Alzheimer's disease (AD), ALS, MS and chronic pain syndromes. (prnewswire.com)
  • Potent, orally active CB1/CB2 receptor agonist with limited brain penetration (EC50 values are 6.1 and 27.9 nM for CB1 and CB2 receptors respectively). (chemspider.com)
  • Cannabidiol (CBD), a major cannabinoid of hemp, does not bind to CB1 receptors and is therefore devoid of psychotomimetic properties. (genengnews.com)
  • Here, we addressed the functional interplay between BDNF and cannabinoid CB 1 receptors (CB 1 Rs) in the striatum, a brain area in which both BDNF and CB 1 s play a role in the emotional consequences of stress and of rewarding experiences. (jneurosci.org)
  • It won't get you high because it doesn't activate CB1 receptors in the brain and central nervous system. (cfah.org)
  • As mentioned earlier, THC can get you high because it activates the CB1 receptors in your brain and nervous system. (cfah.org)
  • Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. (pharmavoice.com)
  • Receptors for LPA are involved in brain development, embryo implantation, and hair growth. (rndsystems.com)
  • Accordingly, CB 1 receptor activation has been reported to suppress nociceptive behavior both in pathological pain states and in healthy organisms ( Pertwee, 2009 ). (frontiersin.org)
  • Cannabinoid receptor agonists protect cultured rat hippocampal neurons. (erowid.org)
  • In conclusion, the present study lends support to the idea that stimulation of CB2 receptors ameliorates several altered parameters in Alzheimer's disease such as impaired memory and learning, neuroinflammation, oxidative stress damage and oxidative stress responses, selected tau kinases, and tau hyperphosphorylation around plaques. (nih.gov)
  • Initial experiments were designed to look at the optimal time of stimulation for both receptors. (bmglabtech.com)
  • The patient was prescribed cannabinoid therapeutics (CT) initially by a physician practicing in Germany, and the prescriptions were later confirmed by a Finnish neurologist. (karger.com)
  • AEA), 2-arachidonoyl glycerol (2-AG) [ 6 ], and more recently the endogenous metabolite of AEA N -arachidonoyl glycine (NAGly) was shown to activate the GPR18, which is a putative cannabinoid receptor [ 7 - 9 ]. (hindawi.com)
  • Because the neurobiological substrate of cariprazine has remained elusive, we took advantage of PharmacoSTORM to provide in vivo evidence that cariprazine predominantly binds to D 3 dopamine receptors on Islands of Calleja granule cell axons but avoids dopaminergic terminals. (nature.com)
  • The switch between TRPV1 and CB 1 receptor activation by the AEA precursor 20:4-NAPE during inflammation may play an important role in nociceptive processing, hence the development of pathological pain. (frontiersin.org)
  • These adaptations with inflammation have important implications for the development of cannabinoid-based pain therapies. (iasp-pain.org)
  • Unlike THC, CBD is a cannabinoid that doesn't make people high and may be useful in reducing pain and inflammation, controlling epileptic seizures, and possibly even treating mental illness and addictions. (pharmavoice.com)
  • Therefore, it is critical to increase our understanding of both cannabinoid addiction and the consequences of cannabinoid use on cognitive and emotional function in adolescence. (nature.com)
  • Dr. Arnold has participated in field investigations pertaining to the epidemic use and health consequences associated with synthetic cannabinoid use. (cdc.gov)
  • The systemic administration of cannabinoid receptor agonists may have important therapeutic implications wherein cannabinoid receptor agonists may reduce morbidity and mortality of oral cancer. (420magazine.com)
  • The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the immune system. (pharmavoice.com)
  • Haloperidol also enhanced BDNF levels in the striatum, suggesting that this neurotrophin may act as a downstream effector of D 2 Rs in the modulation of cannabinoid signaling. (jneurosci.org)
  • CBD modulation of Cys-loop receptors has pharmacological relevance. (researchgate.net)
  • The action of BDNF on CB 1 R (GABA) function was tyrosine kinase dependent and was complete even after receptor sensitization with cocaine or environmental manipulations activating the dopamine (DA)-dependent reward system. (jneurosci.org)
  • The specific CB2 cannabinoid receptor agonist JWH-133 induced cognitive improvement in double AβPP/PS1 transgenic mice, a genetic model of Alzheimer's disease. (nih.gov)
  • Thus, SA of a rewarding cannabinoid in adolescence does not produce long-term cognitive dysfunction. (nature.com)