Receptors, Cannabinoid: 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.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Cannabinoid Receptor Antagonists: Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.Receptor, Cannabinoid, CB2: A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.Cannabinoids: Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.Cannabinoid Receptor Modulators: Compounds that interact with and modulate the activity of CANNABINOID RECEPTORS.Pyrazoles: 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.Piperidines: A family of hexahydropyridines.Cannabinoid Receptor Agonists: Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.Endocannabinoids: 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.Dronabinol: 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.Receptors, Drug: 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.Benzoxazines: OXAZINES with a fused BENZENE ring.BornanesPolyunsaturated Alkamides: 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.Cyclohexanols: 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.Naphthalenes: 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.Arachidonic AcidsMorpholinesDose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Glycerides: GLYCEROL esterified with FATTY ACIDS.Rats, Sprague-Dawley: 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.Cannabidiol: Compound isolated from Cannabis sativa extract.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.AmidohydrolasesMonoacylglycerol Lipases: An enzyme that catalyzes the hydrolysis of glycerol monoesters of long-chain fatty acids EC 3.1.1.23.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Cannabinol: A physiologically inactive constituent of Cannabis sativa L.Cannabis: 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.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Indoles: 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.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Mice, Inbred C57BLCalcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Neurons: 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.Ligands: 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)Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Signal Transduction: 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.Behavior, Animal: The observable response an animal makes to any situation.Mice, Knockout: 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.Histamine H2 Antagonists: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Serotonin 5-HT3 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.Carbamates: 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.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Dopamine Antagonists: Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.Synaptic Transmission: 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.Brain: 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.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Drug Inverse Agonism: 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.Cells, Cultured: 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.Guanosine 5'-O-(3-Thiotriphosphate): 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.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Hippocampus: 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.CHO Cells: 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.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.TRPV Cation Channels: 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.Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.Binding, Competitive: 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.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Disease Models, Animal: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Hallucinogens: 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.Benzodioxoles: Compounds based on benzene fused to oxole. They can be formed from methylated CATECHOLS such as EUGENOL.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Mice, Inbred ICRHyperalgesia: 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.Drug Tolerance: 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.Receptors, Opioid, mu: 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.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Marijuana Abuse: The excessive use of marijuana with associated psychological symptoms and impairment in social or occupational functioning.Ethanolamines: AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Cyclohexanes: Six-carbon alicyclic hydrocarbons.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.ResorcinolsPatch-Clamp Techniques: 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.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.Receptors, Opioid: 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.Excitatory Postsynaptic Potentials: Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Cyclic AMP: 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.Pertussis Toxin: 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.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Cerebellum: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.Biphenyl CompoundsNaloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Substance Withdrawal Syndrome: Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Injections, Intraventricular: Injections into the cerebral ventricles.Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.Leukotriene Antagonists: A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.Benzofurans: Compounds that contain a BENZENE ring fused to a furan ring.Receptor, Endothelin A: A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.Pain Measurement: 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.Receptors, Serotonin: Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.Receptors, Dopamine D2: 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.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Serotonin 5-HT1 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.Periaqueductal Gray: Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain.Sulfonamides: A group of compounds that contain the structure SO2NH2.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents).Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Receptors, Opioid, kappa: 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.Benzazepines: Compounds with BENZENE fused to AZEPINES.Phenylmethylsulfonyl Fluoride: An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex.Gastrointestinal Motility: The motor activity of the GASTROINTESTINAL TRACT.Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Xanthines: Purine bases found in body tissues and fluids and in some plants.Marijuana Smoking: Inhaling and exhaling the smoke from CANNABIS.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.Palmitic Acids: A group of 16-carbon fatty acids that contain no double bonds.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Benzamides: BENZOIC ACID amides.GTP-Binding Protein alpha Subunits, Gi-Go: A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.TetrazolesPyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.Amygdala: Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Cimetidine: A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.Conditioning, Operant: Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced.Serotonin Receptor Agonists: 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.Cholecystokinin: A peptide, of about 33 amino acids, secreted by the upper INTESTINAL MUCOSA and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.TritiumSynapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Rats, Long-Evans: An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.Anisoles: A group of compounds that are derivatives of methoxybenzene and contain the general formula R-C7H7O.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Pain Threshold: Amount of stimulation required before the sensation of pain is experienced.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Receptors, Metabotropic Glutamate: Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Interneurons: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.Histamine H3 Antagonists: Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the AMYGDALA; EPITHALAMUS; GYRUS CINGULI; hippocampal formation (see HIPPOCAMPUS); HYPOTHALAMUS; PARAHIPPOCAMPAL GYRUS; SEPTAL NUCLEI; anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)).Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Autoradiography: The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Designer Drugs: Drugs designed and synthesized, often for illegal street use, by modification of existing drug structures (e.g., amphetamines). Of special interest are MPTP (a reverse ester of meperidine), MDA (3,4-methylenedioxyamphetamine), and MDMA (3,4-methylenedioxymethamphetamine). Many drugs act on the aminergic system, the physiologically active biogenic amines.Adrenergic alpha-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.Nociceptors: Peripheral AFFERENT NEURONS which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the DORSAL ROOT GANGLIA. Their peripheral terminals (NERVE ENDINGS) innervate target tissues and transduce noxious stimuli via axons to the CENTRAL NERVOUS SYSTEM.Animals, Newborn: Refers to animals in the period of time just after birth.Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.6-Cyano-7-nitroquinoxaline-2,3-dione: A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.Inhibitory Postsynaptic Potentials: Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Body Temperature: The measure of the level of heat of a human or animal.Heroin: A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed)Enkephalin, Ala(2)-MePhe(4)-Gly(5)-: An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.Medical Marijuana: Product of the CANNABIS plant, CANNABINOIDS, or synthetic derivatives thereof, used in the treatment of a wide range of clinical symptoms.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.GABA-B Receptor Antagonists: Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.Maze Learning: Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)
Agents with orexigenic effects include the following: 5-HT2C receptor antagonists/inverse agonists - mirtazapine, olanzapine, ... natural or synthetic cannabinoids, first-generation antihistamines, most antipsychotics and many steroid hormones. ... and pralmorelin MC4 receptor antagonists Insulin Sugars such as fructose Anorectic (anorexigenic) Anorexia Eating disorder ... clonidine CB1 receptor agonists (cannabinoids - THC/dronabinol (a component of Cannabis), nabilone Corticosteroids - ...
... is among the first of a new generation of cannabinoid receptor antagonist designed to avoid the central nervous system ... TM-38837 is a small molecule inverse agonist/antagonist of the CB1 cannabinoid receptor, with peripheral selectivity. It is ... 1H-pyrazole-3-carboxamide as a Potential Peripheral Cannabinoid-1 Receptor Inverse Agonist". ChemMedChem. 5 (9): 1439-1443. doi ... liabilities of the first generation CB1 receptor antagonists such as rimonabant. AM-6545 https://web.archive.org/web/ ...
Zotepine Alpha-adrenergic agonist Clonidine Guanfacine Cannabinoids Cannabidiol Tetrahydrocannabinol Orexin receptor antagonist ... First-generation Chlorpromazine Second-generation Clozapine Olanzapine Quetiapine Risperidone ... H1 antagonists are used to treat certain allergies. Sedation is a common side-effect, and some H1 antagonists, such as ... Second-generation antihistamines cross the blood-brain barrier to a much lower degree than the first ones.[medical citation ...
... modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor ... A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of ... cannabinoid receptor 1 (CB1) and 2 (CB2). Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit ... This revived the research on cannabinoid receptor antagonists which were expected to help answer these questions. The use of ...
... modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor ... A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of ... cannabinoid receptor 1 (CB1) and 2 (CB2). Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit ... 1994), "SR141716A, a potent and selective antagonist of the brain cannabinoid receptor", FEBS Letters, 350 (2-3): 240-244, doi: ...
See also: cannabinoid receptor type 1 ligands, cannabinoid receptor type 2 ligands Cannabinoid receptor antagonist ... reactive oxygen species generation, cell death, and cardiovascular inflammatory response both in vitro, as well as in models of ... GPR119 has been suggested as a fifth possible cannabinoid receptor. Cannabinoid receptors are activated by cannabinoids, ... Cannabinoid receptors are of a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of ...
The reason behind the antitumor effect of HU-331 appears unknown as cannabinoid receptor antagonists do not inhibit HU-331, ... The doxorubicin damages DNA by intercalation, the generation of reactive oxygen species and inhibition of DNA topoisomerase I ... The growth of glioma is inhibited by a selective activation of the CB2 cannabinoid receptor and endogenous cannabinoids such as ... Cannabinoids can act as anticancer compounds killing several oncogenic cells followed by direct interaction with cannabinoid ...
There exist two primary CNS cannabinoid receptors, on which marijuana and the cannabinoids act. Both the CB1 receptor and CB2 ... Because of the possible role of serotonin in sleep patterns, a new generation of 5-HT2 antagonists are in current development ... All proven antipsychotics are postsynaptic dopamine receptor blockers (dopamine antagonists). For an antipsychotic to be ... Second-generation (atypical) antipsychotics: The concept of "atypicality" is from the finding that the second generation ...
"Differential response to a selective cannabinoid receptor antagonist (SR141716: rimonabant) in female mice from lines ... After 200 generations, they used E&R approach to identify genomic regions that were selected by natural selection in the ... Organisms with longer generations times, although costly, can be used in experimental evolution. Laboratory studies with foxes ... Bacteria have short generation times, easily sequenced genomes, and well-understood biology. They are therefore commonly used ...
Differential response to a selective cannabinoid receptor antagonist (SR141716: rimonabant) in female mice from lines ... I. Adaptation and Divergence During 2,000 Generations". The American Naturalist. 138 (6): 1315-1341. doi:10.1086/285289. ISSN ... I. Adaptation and divergence during 2,000 generations". American Naturalist. 138: 1315-1341. doi:10.1086/285289.. ... Phenotypic and genomic evolution during a 20,000-generation experiment with the bacterium Escherichia coli". Plant Breeding ...
2016: The marijuana receptor-human Cannabinoid receptor type 1 (CB1) and the human C-C chemokine receptor type 2 (CCR2) In ... 2014: The human P2Y receptor 12 (P2Y12) bound to antagonist or agonist; the human Delta opioid receptor at 1.8A and the first ... and on ways to use this scaffold for next generation protein therapeutics. In parallel to the work on botulinum toxin, Stevens ... 2013: Serotonin receptors 5-HT1B and 5-HT2B, the second HIV co-receptor, C-C chemokine receptor type 5 (CCR5) and the first ...
... human clinical trials with neuroprotectants such as NMDA receptor antagonists were unsuccessful.[citation needed] On October 7 ... The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage ... Excess calcium entry overexcites cells and causes the generation of harmful chemicals like free radicals, reactive oxygen ... Glutamate stimulates AMPA receptors and Ca2+-permeable NMDA receptors, which open to allow more calcium into cells. ...
Szallasi A, Appendino G (May 2004). "Vanilloid receptor TRPV1 antagonists as the next generation of painkillers. Are we putting ... "The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia ... Wu C, Gavva NR, Brennan TJ (June 2008). "Effect of AMG0347, a transient receptor potential type V1 receptor antagonist, and ... Vanilloid receptor TRPV Vanilloid receptor subtype 1 TRPV1 Transient receptor potential channel Capsaicin Capsazepine ...
... is a tetrameric ionotropic receptor; alterations in equilibrium between constituent subunits are seen in mGlu2/5HT2A antagonist ... though results are mixed here as anandamide also is a cannabinoid and as such displays some psychotomimetic effect. However, a7 ... techniqes passed on though generations. However, the genetic component is the primary source of the neurological abnormalities ... as such this receptor is of interest in schizophrenia. Agonists at either constituent receptor may modulate the other receptor ...
Mice lacking the mu opioid receptor exhibited a lack of conditioned place preference. Knockouts of CB1 cannabinoid receptor ... Reinstatement of conditioned place preference has shown to be blocked when antagonists for CRH receptors are injected into the ... Role of gustatory and postingestive actions of sweeteners in the generation of positive affect as evaluated by place preference ... Behav Brain Res (in press) Meisel RL, Joppa MA, Rowe RK (1996) Dopamine receptor antagonists attenuate conditioned place ...
NMDA-receptor antagonists[edit]. In a double-blind, placebo-controlled, proof-of-concept study, researchers administered an N- ... The risk of tardive dyskinesia appears to be lower in second-generation antipsychotics than in first-generation antipsychotics ... The role of cannabinoids[edit]. Acute cannabis intoxication transiently produces perceptual distortions, psychotic symptoms and ... methyl-d-aspartate-receptor antagonist (ketamine) to 18 patients already on treatment with lithium (10 patients) or valproate ( ...
... generation can also occur through breakdown of complex sphingolipids that are ultimately broken down into sphingosine ... Velasco, G; Galve-Roperh, I; Sánchez, C; Blázquez, C; Haro, A; Guzmán, M (2005). "Cannabinoids and ceramide: Two lipids acting ... Ceramides induce skeletal muscle insulin resistance when synthesized as a result of saturated fat activation of TLR4 receptors ... "Ceramides and glucosylceramides are independent antagonists of insulin signaling". Cell. 289 (2): 723-734. doi:10.1074/jbc. ...
Similarly, the appetite suppressant rimonabant (a cannabinoid receptor antagonist) had to be withdrawn when it was linked with ... "Binge eating disorder: The next generation of research". International Journal of Eating Disorders. 46 (3): 193-207. doi ... such as the leptin receptor and the MC-4 receptor) or are still awaiting characterization - Prader-Willi syndrome - in addition ...
Similarly, the appetite suppressant rimonabant (a cannabinoid receptor antagonist) had to be withdrawn when it was linked with ... April 2013). "Binge eating disorder: The next generation of research". International Journal of Eating Disorders. 46 (3): 193- ... opioids and cannabinoids and their action receptors inside the brain, DA, muscarinic and MOR and CB1 receptors respectively. ... such as the leptin receptor and the MC-4 receptor) or are still awaiting characterization - Prader-Willi syndrome - in addition ...
... direct-acting Antagonist and indirect-acting Antagonists: Direct-acting antagonist- which takes up space present on receptors ... while their target receptor, cannabinoid receptor 1 (CB1), is presynaptic. The cannabis plant contains Δ9-tetrahydrocannabinol ... are less efficient than human CYP2D6 for the generation of dopamine from p-tyramine. The Km values of the CYP2D isoforms are as ... An irreversible antagonist binds so strongly to the receptor as to render the receptor unavailable for binding to the agonist. ...
Cannabinoids (e.g., cannabis, dronabinol, nabilone). *NMDA receptor antagonists (e.g., ketamine, dextromethorphan, methadone) ... There may also be a decrease in potassium channels which would normally oppose action potential generation. Each of these ... The d-isomer does not have opioid agonist action and acts as an NMDA receptor antagonist; d-methadone is analgesic in ... it activates receptor kinases that increase receptor trafficking and post-translationally modify receptors causing changes in ...
... dopamine antagonists, antihistamines, cholinergics, anticholinergics, emetics, cannabinoids, and 5-HT (serotonin) antagonists. ... H2-receptor antagonists, cytoprotectants, prostaglandin analogues Lower digestive tract: laxatives, antispasmodics, ... A second generation of antibiotics was introduced in the 1940s: aureomycin and chloramphenicol. Aureomycin was the best known ... Leukotriene antagonists androgens, antiandrogens, estrogens, gonadotropin, corticosteroids, human growth hormone, insulin, ...
A second generation of soft corticosteroids such as etiprednol dicloacetate is in development for a full spectrum of other ... soft cannabinoids, soft Ca2+ channel blockers (see for a recent review). Following the introduction of the CDS concepts, work ... or at higher activity at the site of action Receptor-based transient anchor-type (e.g., lung-targeting) CDSs: provide enhanced ... Ca2+ antagonists (felodipine), MAO inhibitors, NSAIDs and neuropeptides (tryptophan, Leu-enkephalin analogs, TRH analogs, ...
It is found that the anti-inflammatory lipid lipoxin A4 is an endogenous allosteric enhancer of the CB1 cannabinoid receptor. ... LXA4 and 15-epi-LXA4 are also high affinity antagonists of the Cysteinyl leukotriene receptor 1 for which leukotrienes (LT) ... superoxide generation, NF-κB activation, and/or generation of pro-inflammatory cytokines (e.g. IL8, IL13, IL12, and IL5) by ... FPR2, which is now termed the ALX, ALX/FPR, or ALX/FPR2 receptor, is a G protein coupled receptor initially identified as a ...
Cusack B, Nelson A, Richelson E (1994). "Binding of antidepressants to human brain receptors: focus on newer generation ... imipramine is an antagonist of the histamine H1 receptors. BDNF: BDNF is implicated in neurogenesis in the hippocampus, and ... "Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys". Psychopharmacology. 222 (3): 425 ... Sigma receptor: activity on sigma receptors is present, but it is very weak (Ki = 520 nM) and it is about half that of ...
The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene. It is closely related to the cannabinoid receptor type 1, which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic-inhibition, the psychoactive properties of tetrahydrocannabinol, the active agent in cannabis, and other phytocannabinoids (plant cannabinoids). The principal endogenous ligand for the CB2 receptor is 2-arachidonoylglycerol (2-AG). CB2 was cloned in 1993 by a research group from Cambridge looking for a second cannabinoid receptor that could explain the pharmacological ...
The actions of THC result from its partial agonist activity at the cannabinoid receptor CB1 (Ki = 10 nM[20]), located mainly in the central nervous system, and the CB2 receptor (Ki = 24 nM[20]), mainly expressed in cells of the immune system.[21] The psychoactive effects of THC are primarily mediated by the activation of cannabinoid receptors, which result in a decrease in the concentration of the second messenger molecule cAMP through inhibition of adenylate cyclase.[22]. The presence of these specialized cannabinoid receptors in the brain led researchers to the discovery of endocannabinoids, such as anandamide and 2-arachidonoyl glyceride (2-AG). THC targets receptors in a manner far less selective than endocannabinoid molecules released during retrograde ...
... (PEA) is an endogenous fatty acid amide, belonging to the class of nuclear factor agonists. PEA has been demonstrated to bind to a receptor in the cell-nucleus (a nuclear receptor) and exerts a great variety of biological functions related to chronic pain and inflammation. The main target is thought to be the peroxisome proliferator-activated receptor alpha (PPAR-α). PEA also has affinity to cannabinoid-like G-coupled receptors GPR55 and GPR119. PEA cannot strictly be considered a classic endocannabinoid because it lacks affinity for the cannabinoid receptors CB1 and CB2. However, the presence of PEA (and other structurally related N-acylethanolamines) has been known to enhance anandamide activity by an "entourage effect". Several papers have demonstrated that an imbalance of the ...
... is activated by the plant cannabinoids Δ9-THC,[12] and the endocannabinoids anandamide, 2-AG, noladin ether in the low nanomolar range. The synthetic cannabinoid CP-55940 is also able to activate the receptor[12] while the structurally unrelated cannabinoid mimic WIN 55,212-2 fails to activate the receptor.[10] Recent research suggests that lysophosphatidylinositol and its 2-arachidonoyl derivative, 2-arachidonoyl lysophosphatidylinositol (2-ALPI), may be the endogenous ligands for GPR55,[13][14][15] and the receptor appears likely to be a possible target for treatment of inflammation and pain as with the other cannabinoid receptors.[16][17]. This profile as a distinct non-CB1/CB2 receptor which responds to a variety of both endogenous and exogenous ...
Endocannabinoids serve as intercellular 'lipid messengers', signaling molecules that are released from one cell and activating the cannabinoid receptors present on other nearby cells. Although in this intercellular signaling role they are similar to the well-known monoamine neurotransmitters such as dopamine, endocannabinoids differ in numerous ways from them. For instance, they are used in retrograde signaling between neurons. Furthermore, endocannabinoids are lipophilic molecules that are not very soluble in water. They are not stored in vesicles and exist as integral constituents of the membrane bilayers that make up cells. They are believed to be synthesized 'on-demand' rather than made and stored for later use. The mechanisms and enzymes underlying the biosynthesis of endocannabinoids remain elusive and continue to be ...
The CB1 receptor is a pre-synaptic heteroreceptor that modulates neurotransmitter release when activated in a dose-dependent, stereoselective and pertussis toxin-sensitive manner.[13] The CB1 receptor is activated by cannabinoids, generated naturally inside the body (endocannabinoids) or introduced into the body as cannabis or a related synthetic compound. Research suggests that the majority of CB1 receptors are coupled through Gi/o proteins. Upon activation, CB1 receptor exhibits its effects mainly through activation of Gi, which decreases intracellular cAMP concentration by inhibiting its production enzyme, adenylate cyclase, and increases mitogen-activated protein kinase (MAP kinase) concentration. Alternatively, in some rare cases CB1 receptor activation may be coupled to Gs proteins, which stimulate adenylate cyclase.[10] cAMP is known ...
... is a drug that acts as a potent and moderately selective agonist for the cannabinoid receptor CB1, with around 19x selectivity for CB1 over the related CB2 receptor.[1] It was originally invented in the early 1990s by a team led by Thomas D'Ambra at Sterling Winthrop,[2] but has subsequently been researched by many others, most notably the team led by Alexandros Makriyannis at the University of Connecticut. The (piperidin-2-yl)methyl side chain of AM-1220 contains a stereocenter, so there are two enantiomers with quite different potency, the (R) enantiomer having a Ki of 0.27nM at CB1 while the (S) enantiomer has a much weaker Ki of 217nM.[3] A number of related compounds are known with similar potent cannabinoid activity, with modifications such as substitution of the indole ring at the 2- or 6- positions, the naphthoyl ring substituted at the 4- position or replaced by substituted benzoyl rings or ...
Primary research on the functioning of the CB2 receptor has focused on the receptor's effects on the immunological activity of leukocytes.[37] To be specific, this receptor has been implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, and induction of cell migration.[6] Through their inhibition of adenylyl cyclase via their Gi/Goα subunits, CB2 receptor agonists cause a reduction in the intracellular levels of cyclic adenosine monophosphate (cAMP).[38][39] Although the exact role of the cAMP cascade in the regulation of immune responses is currently under debate, laboratories have previously demonstrated that inhibition of adenylyl cyclase by CB2 receptor agonists results in a reduction in the binding of transcription factor CREB (cAMP response element-binding protein) to DNA.[37] This reduction causes changes in the expression of critical immunoregulatory genes[38] and ...
... (part of the AM cannabinoid series) is an analgesic drug which is a cannabinoid agonist. It is conformationally restricted by virtue of the double bond on its side chain, leading an increased affinity for and selectivity between CB1 and CB2 receptors.[1] It is a potent and reasonably selective agonist for the CB1 cannabinoid receptor, with a Ki of 1.2 nM at CB1 and 5.3 nM at CB2.[2] ...
... is a drug which is a cannabinoid derivative that is used in scientific research. It is described as a mixed agonist/antagonist at the cannabinoid receptor CB1, meaning that it acts as an antagonist when co-administered alongside a more potent CB1 agonist, but exhibits weak partial agonist effects when administered by itself.[1][2] ...
... (part of the AM cannabinoid series) is an analgesic drug which is a cannabinoid agonist. It is a derivative of Δ8THC substituted with a dithiolane group on the 3-position side chain.[1] AMG-3 is a potent agonist at both CB1 and CB2 receptors with a Ki of 0.32nM at CB1 and 0.52nM at CB2,[2][3] and its particularly high binding affinity has led to it being used as a template for further structural development of novel cannabinoid drugs.[4] It has sedative and analgesic effects, with analgesia lasting for up to 36 hours after administration.[5] ...
G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the GPR119 gene. GPR119, along with GPR55 and GPR18, have been implicated as novel cannabinoid receptors. GPR119 is expressed predominantly in the pancreas and gastrointestinal tract in rodents and humans, as well as in the brain in rodents. Activation of the receptor has been shown to cause a reduction in food intake and body weight gain in rats. GPR119 has also been shown to regulate incretin and insulin hormone secretion. As a result, new drugs acting on the receptor have been suggested as novel treatments for obesity and diabetes. A number of endogenous and synthetic ligands for this receptor have been identified: 2-Oleoylglycerol Anandamide AR-231,453 MBX-2982 Oleoylethanolamide (Endogenous Ligand) PSN-375,963 PSN-632,408 GRCh38: Ensembl release 89: ...
... is an analgesic drug that is a cannabinoid agonist. It is a highly selective agonist for the CB2 receptor, with selectivity of 414x for CB2 over CB1,[1] although it is still not as selective as newer agents such as HU-308. It produces some similar effects to other cannabinoid agonists such as analgesia, but with little or no sedative or psychoactive effects due to its weak CB1 activity, and a relatively strong antiinflammatory effect due to its strong activity at CB2.[2][3] ...
Generation of Baculovirus.. Full-length human MRP1, MRP2, and MRP3 were cloned separately into the Gateway pDONR221vector. The ... 2009) Cannabinoid receptor CB1 antagonists: state of the art and challenges. Vitam Horm 81:159-189. ... Cannabinoid type 1 (CB1) receptor antagonists have been developed for the treatment of obesity, but a major disadvantage is ... 4-diarylpyrazoline CB1 receptor antagonists (Fig. 1) (Lange et al., 2005) and the prototypic CB1 receptor antagonist rimonabant ...
... modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor ... A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of ... cannabinoid receptor 1 (CB1) and 2 (CB2). Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit ... 1994), "SR141716A, a potent and selective antagonist of the brain cannabinoid receptor", FEBS Letters, 350 (2-3): 240-244, doi: ...
... modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor ... A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of ... cannabinoid receptor 1 (CB1) and 2 (CB2). Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit ... This revived the research on cannabinoid receptor antagonists which were expected to help answer these questions. The use of ...
9:10 TM38837 - A second generation peripheral selective CB1 receptor antagonist. Christian Elling, Director, Molecular ... Pharmacological blockage of the cannabinoid 1 (CB1) receptor is efficacious in obesity and type 2 diabetes ... immune therapy in type I diabetes and receptor agonists are just some of the topics being covered. Speakers will include ...
Unfortunately, first generation inverse agonists of CB1R have serious psychiatric side effects and are no longer in clinical ... However, neutral antagonists or CNS-sparing peripherally restricted antagonists of CB1R may be useful for ALD as these ... Past reports suggest that antagonism of the CB1 receptor (CB1R) is an emerging strategy to alcoholic liver disease. ... Inhibition of alcoholic steatosis by a type 1 cannabinoid receptor antagonist ESBRA 2015 Meeting Abstract P-16. ...
Towards Next Generation Adenosine A2A Receptor Antagonists. , 2014; 21(34): 3918 - 3935. G. Yuan and G.B. Jones. DOI: 10.2174/ ... Cannabinoid Receptor Type 2 Activation in Atherosclerosis and Acute Cardiovascular Diseases. , 2014; 21(35): 4046 - 4058. ... Targeting the Mannose Receptor with Mannosylated Subunit Vaccines. , 2014; 21(30): 3405 - 3418. B. Sedaghat, R. Stephenson and ...
... including palonosetron a second-generation 5-HT3 receptor antagonist and aprepitant NK-1 antagonist to manage moderate to high ... Cannabinoids and benzodiazepines are few other potentially effective drugs. In spite of all these an extensive continuous ... On the basis of receptor antagonist, the market is segmented into serotonin receptor antagonists (5-HT3RAs), which block the ... serotonin receptor; neurokinin-1 receptor antagonists, which block the substance P receptor and corticosteroids. These drugs ...
Project From Peripheralized to Cell- and Organelle-Targeted Medicine: The 3rd Generation of Cannabinoid-1 Receptor Antagonists ... Summary Clinical experience with globally-acting cannabinoid-1 receptor (CB1R) antagonists revealed the benefits of blocking ... Clinical experience with globally-acting cannabinoid-1 receptor (CB1R) antagonists revealed the benefits of blocking CB1Rs for ... children in Generation R Study (in utero - 18 yrs); parents in Generation R Study (18-45 yrs); and the Rotterdam Study (45 yrs ...
Project From Peripheralized to Cell- and Organelle-Targeted Medicine: The 3rd Generation of Cannabinoid-1 Receptor Antagonists ... Summary Clinical experience with globally-acting cannabinoid-1 receptor (CB1R) antagonists revealed the benefits of blocking ... Clinical experience with globally-acting cannabinoid-1 receptor (CB1R) antagonists revealed the benefits of blocking CB1Rs for ... Thematically, our studies focus on a novel class of receptors previously not considered. Based on the receptors ability to act ...
... develops new generations of peripherally-restricted cannabinoid-1 receptor (CB1) inverse agonists/ antagonists f... ...
Endogenous Cannabinoid Receptor Type 1(CB1) and so on) and the SGAs-induced glucose and lipid metabolic disorder in Chinese Han ... Serotonin Antagonists. Serotonin Agents. Neurotransmitter Agents. Molecular Mechanisms of Pharmacological Action. Physiological ... Genes Polymorphisms and Metabolic Effects of the Second Generation Antipsychotic Drugs in Patients With Schizophrenia. The ... The purpose of the study is to investigate these effects of Second-Generation Antipsychotic (SGAs) on glucose and lipid ...
... we have performed pre-treatments with receptor antagonists for the cannabinoid receptors (SR141716A and AM630) or for the ... including genes coding for the kinases responsible of tau phosphorylation and for the secretases involved in Aβ generation. In ... In order to understand through which receptor CBD exerted these effects, ... vanilloid receptor 1 (TRPVI). Here, we have proved that TRPV1 was able to mediate the modulatory effect of CBD on the PI3K/Akt/ ...
Agents with orexigenic effects include the following: 5-HT2C receptor antagonists/inverse agonists - mirtazapine, olanzapine, ... natural or synthetic cannabinoids, first-generation antihistamines, most antipsychotics and many steroid hormones. ... and pralmorelin MC4 receptor antagonists Insulin Sugars such as fructose Anorectic (anorexigenic) Anorexia Eating disorder ... clonidine CB1 receptor agonists (cannabinoids - THC/dronabinol (a component of Cannabis), nabilone Corticosteroids - ...
"Cannabinoids inhibit excitatory inputs to neurons in the shell of the nucleus accumbens: an in vivo electrophysiological study ... CB1 cannabinoid receptor antagonist‐induced opiate withdrawal in morphine‐dependent rats. Navarro, Navarro; Chowen, Chowen; ... BLA or PFC stimulation induced generation of action potentials in NAc neurons. This excitatory effect was strongly inhibited by ... Distribution of neuronal cannabinoid receptor in the adult rat brain: a comparative receptor binding radioautography and in ...
CB1 antagonist), 3) AM404 (anandamide uptake inhibitor), and 4) cannabidiol (indirect CB1/CB2 receptor antagonist, among other ... CB1 antagonist), (3) AM404 (anandamide uptake inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among ... The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, ... The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition of startle (PPI), ...
Generation of CB1 Receptor Mutants Because previous studies have demonstrated that in ligand displacement assays ORG27569 can ... Our previous combined mutation cycle/modeling studies have identified the binding site of the CB1 antagonist, SR141716A (21, 22 ... Keywords: Allosteric Regulation, Cannabinoid Receptors, Cannabinoids, G Protein-coupled Receptors (GPCR), Signaling ... Song Z. H., Bonner T. I. (1996) A lysine residue of the cannabinoid receptor is critical for receptor recognition by several ...
Combinations comprising alpha-2-delta ligands and nmda receptor antagonists. WO2006113568A2. 13 april 2006. 26 okt 2006. Alza ... Tetrahydrocannabinol (THC) and some other cannabinoids, either from the Cannabis sativa plant or synthetic, have analgesic ... All compounds including positive control compounds are serially diluted in the solution of NADPH generation system to give ... Three general GABA receptors have been identified, GABAA, GABAB and GABAC. GABAA and GABAC are ionotropic receptors, whereas ...
Compounds in preclinical development -- Neuropeptide and kinin antagonists / R. G. Hill, K.R. Oliver -- Glutamate receptor ... Part I. Introduction -- Peripheral and central mechanism of pain generation / H.G. Schaible -- Part II. Drugs in clinical use ... 7 Marijuana and cannabinoids for pain -- 8 Adjuvant agents in chronic pain therapy -- 9 Complications of opioid therapy -- 10 ... Future targets in analgesia research -- Adenosine and ATP receptors / J. Sawynok -- Ion channels in analgesia research / J.N. ...
Interestingly, the ORL1 receptor seems to respond to cannabinoids, or TRPV1 active compounds. That is why they hope maybe it ... Are ORL1 antagonists the answer. Who knows. Let us know if suboxone works for you. I doubt you will find very many with central ... This causes the brain to function as an organ of pain generation, but not in a coordinated fashion, a disintegrated fashion. ... The common opioid receptors are mu, delta, kappa, and the ORL1 (aka nociceptin) receptor, which is the latest discovered. This ...
... and is blocked by the cannabinoid receptor antagonist AM251, indicating that it is mediated by the autocrine release of ... support generation of such rhythms. In order to study the regulation of intrathalamic rhythm generation and the effects of GA ... The inward and outward currents were blocked by a 5-HT(3) receptor antagonist, tropisetron, and a 5-HT(1A) receptor antagonist ... receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5), suggesting that non-NMDA receptors were predominantly involved in ...
THC and other cannabinoids were shown to induce apoptosis of glioma cells via ceramide generation (24). THC also promoted the ... The effect of CB1 and CB2 receptor antagonists on DC survival/apoptosis. THC binds to both CB1 and CB2 with similar affinities ... The precise role of cannabinoid receptors (CB)1 and CB2, as well as endogenous ligands for these receptors, on immune cells ... Effect of an endogenous cannabinoid on DCs and the role of CB1 or CB2 receptors. To investigate whether endogenous cannabinoids ...
At least one cannabinoid receptor antagonist is on the verge of appro...,Nanotechnology,propels,advances,in,regenerative, ... Other research has shown that the endogenous cannabinoid system helps ... ... "the generation of genetic or pharmacological tools that selectively [interrupt] this pathway." ... Other research has shown that the endogenous cannabinoid system helps ... At least one cannabinoid receptor antagonist is on ...
Abstract The possible role of the CB2 receptor (CB2r) in psychiatric disorders has been considered. Several animal models use ... In addition, it is well known that the systemic administration of receptor antagonists does not mimic the situation of a KO ... The generation of mice with targeted mutation of these genes was focused on the development of genetic models of the putative ... CB2 receptor (CB2r) has been considered the peripheral cannabinoid receptor owing to its presence in the spleen and ...
4 A-D). In contrast, pretreatment with the opioid receptor antagonist naloxone (2 mg/kg, i.p.) failed to reduce any of ... Generation of FAAH−/− Mice.. The FAAH gene was isolated from a 129SvJ genomic library, and a 2.5-kb region encompassing the ... The endogenous cannabinoid system has been the focus of intense research over the past decade (1-3). Cannabinoid receptors that ... central cannabinoid receptor;. FAAH,. fatty acid amide hydrolase;. NAE,. N-acyl ethanolamine;. THC,. tetrahydrocannabinol. ...
The Case for Cannabinoid CB1 Receptors as a Target for Bronchodilator Therapy for β-agonist Resistant Asthma. Current Drug ... Cysteinyl-Leukotriene Receptor Antagonists: Present Situation and Future Opportunities. Current Medicinal Chemistry ... Toll Like Receptors in Copd and Periodontal Disease-A Mini Review. Immunology, Endocrine & Metabolic Agents in Medicinal ... Engineering Approaches to Develop the Next Generation of Antibodies to Respiratory Targets. Author(s): Katherine A. Vousden, ...
  • The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. (frontiersin.org)
  • Inhibition of PLC by U73122, ROCK by Y-27632 and antagonism of inositol trisphosphate (InsP3) receptors by 2-APB abolished OEA vasorelaxation. (elsevier.com)
  • Cannabinoid-induced inhibition of MMP-2 expression and cell invasion was prevented by blocking ceramide biosynthesis and by knocking-down the expression of the stress protein p8. (aacrjournals.org)
  • In addition, several clinical trials are testing other potential palliative properties of cannabinoids in oncology such as appetite stimulation and pain inhibition ( 5 , 6 ). (aacrjournals.org)
  • Studies on malignant gliomas and other models of cancer strongly support the conclusion that cannabinoids decrease tumor progression by at least two mechanisms: the apoptotic death of tumor cells ( 7 - 10 ) and the inhibition of tumor angiogenesis ( 8 , 11 - 14 ). (aacrjournals.org)
  • When aiming to induce hyaline chondrogenic cells right Syk inhibition from dermal fibroblasts, as well as activation of cartilage distinct matrix genes, elimination of expression of form I collagen is required for generation of hyaline cartilage. (phosphorylaseinhibitors.com)
  • To do all that we do, we have to read widely to have a good grasp of protein structure, biophysics, medicinal chemistry, receptor pharmacology and biochemistry. (uncg.edu)
  • Yao et al, 2002), and increased CB1 receptor (CB1r) expression in the dorsolateral prefrontal cortex (PFC) of schizophrenic patients (Dean et al, 2001). (420magazine.com)
  • Recent in vitro evidence suggests that indeed cannabinoids modulate glutamatergic synapses in the NAc. (deepdyve.com)
  • 7 This upregulation correlated with increased reactive oxygen species (ROS) generation in in vitro studies. (acc.org)
  • Antagonists of PRLr kill human breast cancer cells in vitro and abrogate the tumorigenesis in the xenograft models, showing that persistent signaling induced by locally secreted PRL is essential for growth and survival of these cells ( 20 , 21 ). (aacrjournals.org)
  • CB1 receptors are coupled through Gi/o proteins and inhibit adenylyl cyclase and activate mitogen-activated protein (MAP) kinase. (wikipedia.org)
  • In addition, CB1 receptors inhibit presynaptic N- and P/Q-type calcium channels and activate inwardly rectifying potassium channels. (wikipedia.org)
  • Δ9-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. (muscleblog.es)
  • Previously, we identified small molecules that inhibit human TNF by stabilising a distorted trimer and reduce the number of receptors bound to TNF from three to two. (bvsalud.org)
  • Besides these palliative actions, cannabinoids have been proposed as potential antitumoral agents owing to their ability to inhibit the growth and angiogenesis of various types of tumor xenografts in animal models ( 5 ). (aacrjournals.org)
  • It has also been reported that cannabinoids inhibit tumor cell migration and spreading ( 12 , 15 - 18 ). (aacrjournals.org)
  • The therapeutic application of metabolic inhibitors , pharmacotherapy for obesity, immune therapy in type I diabetes and receptor agonists are just some of the topics being covered. (smi-online.co.uk)
  • Human subjects injected with ghrelin remember pictures of food more clearly a day later and inhibitors of the ghrelin receptor could impair those memories [ 5 ]. (hindawi.com)
  • Etoricoxib is a non-steroidal anti-inflammatory drug, from the coxibs group, that represents a second-generation of COX-2 inhibitors, used for the treatment of arthritis and pain. (ufsm.br)
  • Adenosine diphosphate-sensitive P2Y11 receptor inhibits endothelial cell proliferation by induction of cell cycle arrest in the S phase and induces the expression of inflammatory mediators. (bioportfolio.com)
  • However, PRL also induces proteolytic degradation of PRLr via receptor ubiquitination facilitated by the SCF βTrcp E3 ubiquitin ligase that is recruited to the substrate in a manner that requires phosphorylation of Ser349 within the phosphorylated degron ( 22 , 23 ). (aacrjournals.org)
  • Cannabinoid Action Induces Autophagy-Mediated Cell Death Through Stimulation of ER Stress in Human Glioma Cells. (mrnice.nl)
  • As a whole, this study defines COX-2 as a hitherto unknown target by which a cannabinoid induces apoptotic death of glioma cells. (aspetjournals.org)
  • Studies in rodents have shown that antagonism of this receptor leads to reduced food intake and weight reduction ( Boyd and Fremming, 2005 ). (aspetjournals.org)
  • Past reports suggest that antagonism of the CB1 receptor (CB1R) is an emerging strategy to alcoholic liver disease. (rti.org)
  • 11 Further, CB 1 receptor antagonism was shown to reduce PDGF-mediated proliferation and migration of human coronary artery smooth muscle cells. (acc.org)
  • Protons, ie the Hydrogen ion part of HCL from acid, can cause the TRPV1 receptor to fire continually, even without a stimulus being applied to the skin surface. (rutgers.edu)
  • In summary, RTI-13329-173B and other such peripherally selective CB1R antagonists should be further developed and investigated for alcoholic liver disease. (rti.org)
  • Similarly, β3-receptor agonism increased CB1R density in the BAT of rats. (diabetesjournals.org)
  • Conversely, the blockade of CB1R has been found to decrease body weight and fat mass, improve glucose homeostasis and insulin sensitivity, and decrease cardiometabolic risk factors, making CB1R antagonists potential drugs against obesity and diabetes ( 13 ). (diabetesjournals.org)
  • Recently, novel CB1R antagonists, which act strictly peripherally, have been found to activate BAT in rodents, inducing lipolysis and lipid oxidation, thus improving metabolism ( 15 , 16 ). (diabetesjournals.org)
  • Consequently, there is a need for alternate therapy in which other receptors specifically expressed on tumor cells can be targeted to abrogate EGFR-mediated signaling events directly or indirectly. (aacrjournals.org)
  • Our findings suggest the THC promotes tumor growth by inhibiting antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. (jimmunol.org)
  • CB 2 receptor agonists attenuate inflammatory response to tumor necrosis factor alpha and decrease expression of cell adhesion molecules, which are key steps in atherogenesis. (acc.org)
  • 12 The same group of investigators showed that CB 2 receptor agonists JWH-133 and HU-30 decreased tumor-necrosis-factor-alpha-induced proliferation and migration of coronary smooth muscle cells. (acc.org)
  • Of interest, the extent of CB(2) receptor expression was directly related with tumor malignancy. (muscleblog.es)
  • This background prompted us to study the effect of cannabinoid administration on MMP expression by tumor cells and its effect on tumor cell invasion. (aacrjournals.org)
  • The inhibitory action afforded by 2AG and CP55,940 was reversed by N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.eptan-2-yl]5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide (SR144528), a selective cannabinoid 2 (CB(2)) receptor antagonist, and left unchanged by the selective CB(1) antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). (unifi.it)
  • In this project, we aim to further characterize the mechanisms of RNA regulation in T-cell acute lymphoblastic leukemia (T-ALL) to obtain insight in the interplay between RNA generation and RNA decay and its role in leukemia development. (europa.eu)
  • Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptor-dependent and/or independent mechanisms. (springer.com)
  • Here, we review the most recent results generating interest in the field of death mechanisms induced by cannabinoids in cancer cells. (spandidos-publications.com)
  • Overall, the results reported here suggest that the exploration of molecular mechanisms induced by cannabinoids in cancer cells can contribute to the development of safe and effective treatments in cancer therapy. (spandidos-publications.com)
  • It involves Ca 2+ released from InsP3-sensitive endothelial stores by mechanisms involving RhoA kinase and phospholipase C. It is likely that the released Ca 2+ causes NO generation and opening of mainly large-conductance K Ca channels. (elsevier.com)
  • However, direct structural information on the mechanisms of general anaesthetics at their physiological receptor sites is lacking. (bvsalud.org)
  • The final two speakers of the symposium were engineers by training and presented new methods demonstrating how multimodal imaging can be a powerful tool to quantify receptor mechanisms related to serotonergic and dopaminergic drugs. (bap.org.uk)