One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1.
An enzyme that catalyzes the conversion of carbamoyl phosphate and L-aspartate to yield orthophosphate and N-carbamoyl-L-aspartate. (From Enzyme Nomenclature, 1992) EC 2.1.3.2.
One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.
A family of hexahydropyridines.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.
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.
Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.
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.
Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.
Agents inhibiting the effect of narcotics on the central nervous system.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.
An enzyme that catalyzes the formation of beta-aspartyl phosphate from aspartic acid and ATP. Threonine serves as an allosteric regulator of this enzyme to control the biosynthetic pathway from aspartic acid to threonine. EC 2.7.2.4.
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.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
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.
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.
Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.
Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.
The rate dynamics in chemical or physical systems.
An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.
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.
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.
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.
Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.
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.
Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
Purine bases found in body tissues and fluids and in some plants.
Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.
A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.
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.
Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.
A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).
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.
Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2.
A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.
An enzyme that catalyzes the conversion of aspartic acid to ammonia and fumaric acid in plants and some microorganisms. EC 4.3.1.1.
Cell surface proteins that bind amino acids and trigger changes which influence the behavior of cells. Glutamate receptors are the most common receptors for fast excitatory synaptic transmission in the vertebrate central nervous system, and GAMMA-AMINOBUTYRIC ACID and glycine receptors are the most common receptors for fast inhibition.
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.
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.
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.
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.
Cell surface proteins that bind TACHYKININS with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, SUBSTANCE P; NEUROKININ A; and NEUROKININ B.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
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.
Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.
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.
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.
Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.
Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.
Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
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).
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.
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.
AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.
A family of biologically active peptides sharing a common conserved C-terminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors.
One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.
1,4-Diethylene dioxides. Industrial solvents. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), dioxane itself may "reasonably be anticipated to be a carcinogen." (Merck Index, 11th ed)
Cell surface proteins that bind neuropeptide Y with high affinity and trigger intracellular changes which influence the behavior of cells.
A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.
Compounds with BENZENE fused to AZEPINES.
Organic chemicals which have two amino groups in an aliphatic chain.
This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).
Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.
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.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.
A class of cell surface receptors for tachykinins that prefers neurokinin A; (NKA, substance K, neurokinin alpha, neuromedin L), neuropeptide K; (NPK); or neuropeptide gamma over other tachykinins. Neurokinin-2 (NK-2) receptors have been cloned and are similar to other G-protein coupled receptors.
One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.
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.
Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.
A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ B with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the BRONCHI.
The methyl homolog of parathion. An effective, but highly toxic, organothiophosphate insecticide and cholinesterase inhibitor.
A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.
A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.
A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.
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.
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)
A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.
A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.
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.
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.
A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)
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.
A highly selective and specific beta antagonist that is used to characterize beta-adrenoceptors.
A group of compounds that contain the structure SO2NH2.
Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Injections into the cerebral ventricles.
A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.
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.
Elements of limited time intervals, contributing to particular results or situations.
A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.
Peptides composed of between two and twelve amino acids.
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.
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.
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.
An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.
An aspartate aminotransferase found in MITOCHONDRIA.
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.
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.
Use of electric potential or currents to elicit biological responses.
Drugs that selectively bind to and activate alpha adrenergic receptors.
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.
Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.
A subclass of muscarinic receptor that mediates cholinergic-induced contraction in a variety of SMOOTH MUSCLES.
A class of cell surface receptors for tachykinins that prefers neurokinin B (neurokinin beta, neuromedin K) over other tachykinins. Neurokinin-3 (NK-3) receptors have been cloned and are members of the G-protein coupled receptor superfamily. They have been found in the central nervous system and in peripheral tissues.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.
Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
The observable response an animal makes to any situation.
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.
Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.
A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.
An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).
A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent.
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 species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Seven membered heterocyclic rings containing a NITROGEN atom.
Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood.
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.
One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
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.
A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.
Drugs that selectively bind to and activate beta-adrenergic receptors.
Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.
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.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
A group of TETRAHYDRONAPHTHALENES containing a keto oxygen.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.
The monoanhydride of carbamic acid with PHOSPHORIC ACID. It is an important intermediate metabolite and is synthesized enzymatically by CARBAMYL-PHOSPHATE SYNTHASE (AMMONIA) and CARBAMOYL-PHOSPHATE SYNTHASE (GLUTAMINE-HYDROLYZING).
Compounds based on a partially saturated iminoethanophenanthrene, which can be described as ethylimino-bridged benzo-decahydronaphthalenes. They include some of the OPIOIDS found in PAPAVER that are used as ANALGESICS.
A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.
Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.
Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.
Cell surface receptors that bind specific neuropeptides with high affinity and trigger intracellular changes influencing the behavior of cells. Many neuropeptides are also hormones outside of the nervous system.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
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)
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.
Established cell cultures that have the potential to propagate indefinitely.
A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)
Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.
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.
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
A subclass of purinergic P2Y receptors that have a preference for ATP and ADP. The activated P2Y1 receptor signals through the G-PROTEIN-coupled activation of PHOSPHOLIPASE C and mobilization of intracellular CALCIUM.
A specific subtype of muscarinic receptor found in the lower BRAIN, the HEART and in SMOOTH MUSCLE-containing organs. Although present in smooth muscle the M2 muscarinic receptor appears not to be involved in contractile responses.
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.
Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).
Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).
A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
An enzyme that, in the course of pyrimidine biosynthesis, catalyzes ring closure by removal of water from N-carbamoylaspartate to yield dihydro-orotic acid. EC 3.5.2.3.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.
A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.
A selective and potent serotonin-2 antagonist that is effective in the treatment of a variety of syndromes related to anxiety and depression. The drug also improves the subjective quality of sleep and decreases portal pressure.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
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.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES.
Proteins prepared by recombinant DNA technology.
A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ A with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the URINARY BLADDER and UTERUS.
An essential amino acid that is physiologically active in the L-form.
Drugs that bind to and activate dopamine receptors.
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.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
That phase of a muscle twitch during which a muscle returns to a resting position.
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.
A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)
Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.
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.
"Conantokin G is an NR2B-selective competitive antagonist of N-methyl-D-aspartate receptors". Molecular Pharmacology. 58 (3): ... Conantokins act as potent and specific antagonists of the N-methyl-D-aspartate receptor (NMDAR). They are the only naturally- ... "Novel conantokins from Conus parius venom are specific antagonists of N-methyl-D-aspartate receptors". The Journal of ... a novel peptide antagonist to the N-methyl-D-aspartic acid (NMDA) receptor". Neuroscience Letters. 118 (2): 241-4. doi:10.1016/ ...
... selective N‐methyl‐D‐aspartate receptor antagonist". Pharmacology Research & Perspectives. 3 (6): e00198. doi:10.1002/prp2.198 ... to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP- ... Rislenemdaz is a small-molecule antagonist of the NMDA receptor. The NMDA receptor is composed of several subunits, but ... selective NMDA receptor subunit 2B (NR2B) antagonist which is under development by Cerecor in the United States as an ...
"Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5". ... The field of MCC has its roots in the pioneering pharmacological studies of the role of NMDA receptor in long-term potentiation ... receptor, kinase activation, phosphatase regulation), intra-cellular (i.e. dendritic processes), and inter-cellular processes ( ...
July 1988). "CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist". The ... 1990). "CGS 19755: a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant, anxiolytic and anti ... a competitive antagonist at N-methyl-D-aspartate receptors". The Journal of Pharmacology and Experimental Therapeutics. 250 (2 ... "Tolerance to the cataleptic effect of the N-methyl-D-aspartate (NMDA) receptor antagonists in pigeons: cross-tolerance between ...
"7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex". ... is a tool compound that acts as a potent and selective competitive antagonist of the glycine site of the NMDA receptor. It ... In addition to antagonizing the NMDA receptor, 7-CKA also acts as a potent inhibitor of the reuptake of glutamate into synaptic ... "Essential roles of AMPA receptor GluA1 phosphorylation and presynaptic HCN channels in fast-acting antidepressant responses of ...
"Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5". ... "Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl D-aspartate antagonists". Neuroscience ... As mentioned previously, AMPA receptors are the brain's most abundant glutamate receptors and mediate the majority of its ... an antagonist to the NMDA receptor, which prevented LTP in this pathway. Conversely, LTP in the mossy fiber pathway is NMDA ...
"Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5". ... is a noncompetitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck ... "Competitive as well as uncompetitive N-methyl-D-aspartate receptor antagonists affect cortical neuronal morphology and cerebral ... Basile AS, Huang JM, Xie C, Webster D, Berlin C, Skolnick P (December 1996). "N-methyl-D-aspartate antagonists limit ...
"Prevention of levodopa-induced dyskinesias by a selective NR1A/2B N-methyl-D-aspartate receptor antagonist in parkinsonian ... "Prevention of dyskinesia by an NMDA receptor antagonist in MPTP monkeys: effect on adenosine A2A receptors". Synapse (New York ... Besonprodil (CI-1041) is a drug which acts as an NMDA antagonist, selective for the NR2B subunit. It is under development as a ... Barton ME, White HS (March 2004). "The effect of CGX-1007 and CI-1041, novel NMDA receptor antagonists, on kindling acquisition ...
... selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor ... It is a selective NMDA receptor antagonist that competitively inhibits the ligand (glutamate) binding site of NMDA receptors. ... PMID 2552039 Cellular Analog of Differential Classical Conditioning in Aplysia: Disruption by the NMDA Receptor Antagonist DL-2 ... It is useful to isolate the action of other glutamate receptors in the brain, i.e., AMPA and kainate receptors. AP5 can block ...
September 2011). "The selective and competitive N-methyl-D-aspartate receptor antagonist, (-)-6-phosphonomethyl-deca- ... Allen RM, Dykstra LA (July 2001). "N-methyl-D-aspartate receptor antagonists potentiate the antinociceptive effects of morphine ... "Effects of the competitive N-methyl-D-aspartate receptor antagonist, LY235959 [(-)-6-phosphonomethyl-deca-hydroisoquinoline-3- ... "N-methyl-D-aspartate antagonists and WIN 55212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H- ...
... is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (−)-HA-966 is a potent gamma-butyrolactone-like ... The glycine/N-methyl-D-aspartate receptor antagonist activity is specific to the R-(+) enantiomer, whereas the sedative and ... an antagonist at the glycine/N-methyl-D-aspartate receptor". European Journal of Pharmacology. 186 (1): 129-32. doi:10.1016/ ... 3-Amino-1-hydroxy-pyrrolidin-2-one is a molecule used in scientific research as a glycine receptor and NMDA receptor antagonist ...
... an antagonist of NR2B subunit-containing N-methyl-d-aspartate receptors". Experimental Neurology. 163 (1): 239-43. doi:10.1006/ ... Other NR2B subunit-selective antagonists of the NMDA receptor are still under development for depression, such as rislenemdaz ( ... a novel NR2B subunit antagonist of the N-methyl-D-aspartate receptor, on the volume of ischemic brain damage off cytotoxic ... to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP- ...
"7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex". ... "Glycine site N-methyl-D-aspartate receptor antagonist 7-CTKA produces rapid antidepressant-like effects in male rats". Journal ... 7-Hlorokinurenska kiselina (7-CTKA) je antagonist NMDA receptora sa antidepresantskim dejstvom na pacovima.[2][3] ...
Memantine is a clinically well tolerated N-methyl-d-aspartate (NMDA) receptor antagonist-a review of preclinical data». ... mGluR5 antagonist-induced psychoactive properties: MTEP drug discrimination, a pharmacologically selective non-NMDA effect with ... Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal ... The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) ...
... selective and systemically active mGlu5 receptor antagonist". British Journal of Pharmacology. 132 (7): 1423-30. doi:10.1038/sj ... 2001). "Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal ... van der Kam EL, De Vry J, Tzschentke TM (April 2009). "The mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) ... pyridine reduce traumatic neuronal injury in vitro and in vivo by antagonizing N-methyl-D-aspartate receptors". The Journal of ...
Shukla VK, Lemaire S (January 1997). "N-methyl-D-aspartate antagonist activity of alpha- and beta-sulfallorphans" (PDF). The ... "A sigma-1 receptor selective analogue of BD1008. A potential substitute for (+)-opioids in sigma receptor binding assays". ... It acts as a σ1 receptor agonist and NMDA receptor antagonist. It has no significant affinity for the σ2, μ-opioid, or δ-opioid ... As an NMDA receptor antagonist, in vivo, it is approximately twice as potent as dextromethorphan, and five-fold less potent ...
... methyl]-phosphonic acid (NVP-AAM077) acting at recombinant NR1/NR2A and NR1/NR2B N-methyl-D-aspartate receptors: Implications ... PEAQX is a competitive antagonist at the NMDA receptor. Although originally described as 100-fold selective for GluN1/GluN2A ... "5-Phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than ... GluN1/GluN2B receptors, more detailed studies of the Ki of PEAQX revealed it only shows a 5 fold difference in affinity for ...
It was one of the first selective 5-HT6 receptor antagonists to be discovered, and was found through high-throughput screening ... SB-271046 was found to increase levels of the excitatory amino acid neurotransmitters glutamate and aspartate, as well as ... January 1999). "5-Chloro-N-(4-methoxy-3-piperazin-1-yl- phenyl)-3-methyl-2-benzothiophenesulfon- amide (SB-271046): a potent, ... November 2005). "Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT6 receptor antagonists". Bioorganic & ...
Likewise, SP is known to bind to N-methyl-D-aspartate (NMDA) receptors by eliciting excitation with calcium ion influx, which ... Finally NK1R antagonists may also have a role as novel antiemetics and hypnotics. Many selective ligands for NK1 are now ... TAK-637 T-2328 NK1 receptor antagonist Tachykinin receptor Discovery and development of neurokinin 1 receptor antagonists ... NK1 receptor antagonists block responses to a broader range of emetic stimuli than the established 5-HT3 antagonist treatments ...
N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved ... "Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics". J. Neurosci. 16 (1 ... "Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of ... "Entrez Gene: GRIN2D glutamate receptor, ionotropic, N-methyl D-aspartate 2D". Kurschner C, Yuzaki M (Sep 1999). "Neuronal ...
... a selective NR2B receptor antagonist Traxoprodil, a selective NR2B receptor antagonist Toluene - noncompetitive antagonist ... N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. The NMDA receptor channel has been shown ... Glutamate [NMDA] receptor subunit epsilon-2, also known as N-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a ... leading to reduced receptor function Ifenprodil Evt 101, a selective NR2B receptor antagonist. This compound was tested as a ...
Mathiesen O, Imbimbo BP, Hilsted KL, Fabbri L, Dahl JB (August 2006). "CHF3381, a N-methyl-D-aspartate receptor antagonist and ... It acts as a competitive, reversible, and non-selective monoamine oxidase inhibitor, and as a low affinity, non-competitive ... August 2003). "Antinociceptive activity of the N-methyl-D-aspartate receptor antagonist N-(2-Indanyl)-glycinamide hydrochloride ... a putative N-methyl-D-aspartate receptor antagonist". NeuroReport. 13 (16): 2071-4. doi:10.1097/00001756-200211150-00016. PMID ...
The name "NMDA receptor" is derived from the ligand N-methyl-D-aspartate (NMDA), which acts as a selective agonist at these ... Partial agonists : N-methyl-D-aspartic acid (NMDA); NRX-1074; 3,5-dibromo-L-phenylalanine, etc. Antagonists: ketamine, PCP, ... The N-methyl-D-aspartate receptor (NMDA receptor) - a type of ionotropic glutamate receptor - is a ligand-gated ion channel ... The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, or quisqualate receptor) is a ...
... receptors reverses N-Methyl-D-aspartate antagonist-induced alteration of neuronal firing in prefrontal cortex". Biological ... "A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and ... of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor ... CDPPB is a drug used in scientific research which acts as a positive allosteric modulator selective for the metabotropic ...
... relationships of philanthotoxin analogs and polyamines on N-methyl-D-aspartate and nicotinic acetylcholine receptors". The ... Strømgaard K, Jensen LS, Vogensen SB (March 2005). "Polyamine toxins: development of selective ligands for ionotropic receptors ... "Structure and synthesis of a potent glutamate receptor antagonist in wasp venom". Proceedings of the National Academy of ... For example, AMPA receptors lacking the GluA2 subunit are highly sensitive to PhTX-433, whereas receptors containing the GluA2 ...
... the receptor most involved in that process. Excessive amounts of N-methyl-D-aspartate (NMDA), the selective specific agonist of ... and MGS-0039 are drugs that act as a selective antagonist blocking both of the group II metabotropic glutamate receptors, ... other receptors. For example, group I mGluRs are known to increase the activity of N-methyl-D-aspartate receptors (NMDARs), a ... "Metabotropic glutamate receptors negatively coupled to adenylate cyclase inhibit N-methyl-D-aspartate receptor activity and ...
... is an agonist of glutamate receptors, specifically at both the N-methyl-D-aspartate, or NMDA, and trans-ACPD ... Dizocilpine acts as an uncompetitive antagonist at NMDA receptors. Ibotenic acid toxicity comes from activation of the NMDA ... acts as a non-selective glutamate receptor agonist. Because of this, ibotenic acid can be a powerful neurotoxin, and is ... The NMDA receptor functions properly by allowing Ca2+ ions to pass through after activation at the receptor site. The binding ...
... selective and systemically active mGlu5 receptor antagonist". British Journal of Pharmacology. 132 (7): 1423-30. PMC 1572682 . ... pyridine reduce traumatic neuronal injury in vitro and in vivo by antagonizing N-methyl-D-aspartate receptors". The Journal of ... Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons ... MGluR5 antagonists 2-methyl-6-(phenylethynyl)-pyridine and (E)-2-methyl-6-(2-phenylethenyl)- ...
... researchers administered an N-methyl-d-aspartate-receptor antagonist (ketamine) to 18 patients already on treatment with ... The selective estrogen receptor modulator medication tamoxifen has shown rapid and robust efficacy treating acute mania in ... "A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression". Archives of General ... Khan MM (2018-10-08). "Translational Significance of Selective Estrogen Receptor Modulators in Psychiatric Disorders". ...
Several receptors directly interact with ethanol to promote a cascade of signaling. N-methyl-D-aspartate (NMDA) receptors are ... glutamate receptor antagonist on ethanol consumption by genetic drinking rats. Alcohol, 40, 494-497. Hodge, C.W., Miles, M.F., ... SAHA was selective for reducing ethanol seeking but not sucrose seeking. In alcoholics, certain regions of the amygdala are ... Ethanol sensitivity of recombinant human N-methyl-D-aspartate receptors. Neurochem Int. 38, 333-340. Nagy, J. (2004). The NR2B ...
... a positive allosteric modulator at the N-methyl-D-aspartate receptor" (abstract). Molecular Pharmacology. 40 (3): 333-6. PMID ... An α2, α3 and/or α5 selective positive allosteric agonist, like L-838,427 for example, might be useful as an analgesic drug ... Cannabinoid receptor antagonists. *CCR5 receptor antagonists. *Neurokinin 1 receptor antagonists. *5-HT3 antagonists ... The GABAA receptors are made up of subunits which form a receptor complex. Humans have 19 receptor subunits and are classified ...
... subunit of the N-methyl-D-aspartate receptor". The Journal of Biological Chemistry. 276 (1): 693-99. doi:10.1074/jbc.M008085200 ... an effect that was abolished in either the presence of a specific NR2B antagonist or a trk receptor tyrosine kinase inhibitor.[ ... "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A". Proceedings of the ... The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ...
NMDA receptor antagonists (e.g., ketamine, dextromethorphan, methadone). *Opioids (e.g., hydrocodone, morphine, oxycodone, ... and N-methyl-D-aspartate). Inhibitory effects on 5-HT, norepinephrine, and dopamine transporters are weak.[68] Lamotrigine is a ... P-type-selective: ω-Agatoxin IVA. *ω-Agatoxin IVB. *R-type-selective: SNX-482 ... σ receptors, IC50=145μM. Pharmacokinetics[edit]. The pharmacokinetics of lamotrigine follow first-order kinetics, with a half- ...
... subunit of the N-methyl-D-aspartate receptor". The Journal of Biological Chemistry. 276 (1): 693-99. doi:10.1074/jbc.M008085200 ... an effect that was abolished in either the presence of a specific NR2B antagonist or a trk receptor tyrosine kinase inhibitor.[ ... "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A". Proceedings of the ... receptor binding. • neurotrophin TRKB receptor binding. • growth factor activity. Cellular component. • cytoplasm. • ...
... including the AMPA and kainate receptors and, to a lesser extent, the NMDA receptor.[15][16][17][18] It acts as an antagonist ... Aspartic acid (aspartate). *DIDS. *Direct blue 71. *Erythro-4-methyl-L-glutamic acid ... "The Deployment of Intersensory Selective Attention". Clinical Neuropharmacology. 30 (1): 25-38. doi:10.1097/01.WNF. ... See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Metabotropic glutamate receptor modulators ...
Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... Receptor/signaling modulators. GABA receptor modulators. GABAA receptor positive modulators. Ionotropic glutamate receptor ... "Methyl chloroform". Immediately Dangerous to Life and Health Concentrations (IDLH). National Institute for Occupational Safety ... See also: Receptor/signaling modulators • GABA receptor modulators • GABA metabolism/transport modulators ...
The N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in ... "Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than ... Competitive NMDA receptor antagonists[edit]. Competitive NMDA receptor antagonists, which were developed first, are not a good ... Activation of NMDA receptors requires binding of glutamate or aspartate (aspartate does not stimulate the receptors as strongly ...
In addition there is a synergistic effect with endogenous glutamate and N-Methyl-D-aspartate receptor agonists that contribute ... Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... a neurotransmitter in the brain that activates glutamate receptors. Domoic acid has a very strong affinity for these receptors ... The effects of domoic acid have been attributed to several mechanisms, but the one of concern is through glutamate receptors. ...
Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor ... Decanoic acid and the AMPA receptor antagonist drug perampanel act at separate sites on the AMPA receptor, and so it is ... "NMDA receptor activation dephosphorylates AMPA receptor glutamate receptor 1 subunits at threonine 840". J. Neurosci. 27 (48): ...
"Glutathione Is an Endogenous Ligand of Rat Brain N-Methyl-D-Aspartate (NMDA) and 2-Amino-3-Hydroxy-5-Methyl-4- ... Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Glutamate metabolism/transport modulators ... This glutamate in turn acts on mGluR2/3 receptors, and at higher doses of acetylcysteine, mGluR5.[50][51] ...
Receptor antagonists. *ERA (Atrasentan). *Retinoid X receptor (Bexarotene). *Sex steroid (Testolactone). Other/ungrouped. * ... 16%). The drug also increases the QT interval and liver enzymes (alanine transaminase, aspartate transaminase).[2][6] ... 2014). "Abstract PR02: LEE011: An orally bioavailable, selective small molecule inhibitor of CDK4/6- Reactivating Rb in cancer ...
Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... Receptor/signaling modulators. GABA receptor modulators. GABAA receptor positive modulators. Ionotropic glutamate receptor ... methyl chloroform), trichloroethylene) ... Aspartate. *Glutamate. *Homocysteic acid (L-HCA). * ... See also: Receptor/signaling modulators • GABA receptor modulators • GABA metabolism/transport modulators ...
"Paradoxical convulsant action of a novel non-competitive N-methyl-D-aspartate (NMDA) antagonist, tiletamine". Brain Research. ... σ1 receptor, and the dopamine and norepinephrine transporters.[41] These results suggest that PCP is a highly selective ligand ... Phencyclidine is an NMDA receptor antagonist that blocks the activity of the NMDA receptor to cause anaesthesia and analgesia ... an ionotropic glutamate receptor, in rats and in rat brain homogenate.[49][46] As such, PCP is an NMDA receptor antagonist. The ...
Activators: 3-Methyl-GABA. See also. Receptor/signaling modulators GABA receptor modulators GABAA receptor positive modulators ... Orthosteric (competitive) Antagonist bicuculline,[59] gabazine,[69] thujone,[70] flumazenil[71] Uncompetitive antagonist (e.g. ... Glycine receptor agonists. *Biology of obsessive-compulsive disorder. *Peripherally selective drugs. *GABA ... Receptor/signaling modulators GABAA receptor positive modulators GABA metabolism/transport modulators ...
Strychnine is a strong antagonist at ionotropic glycine receptors, whereas bicuculline is a weak one. Glycine is a required co- ... With methyl iodide, the amine becomes quaternized to give betaine, a natural product: H. 3N+. CH. 2COO−. + 3 CH3I → (CH. 3). 3N ... Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... Receptor/signaling modulators. GABA receptor modulators. GABAA receptor positive modulators. Ionotropic glutamate receptor ...
... evidence for N-methyl-D-aspartate-coupled and dopamine reuptake carrier-associated phencyclidine binding sites". Mol. Pharmacol ... Angiotensin II receptor antagonist. *Endothelin receptor antagonist. *NK1 receptor antagonist. *Vasopressin receptor antagonist ... Tiagabine, a selective GABA reuptake inhibitor used as an anticonvulsant in the treatment of epilepsy and seizures. ... A few of the selective serotonin reuptake inhibitors (SSRIs) such as the dextro-enantiomer of citalopram appear to be ...
... and NMDA receptor antagonist[10] that crosses the blood-brain barrier.[11] Acetylcholinesterase is an enzyme that catalyzes the ... Huperzine A treatment protects against N-methyl-d-aspartate-induced seizure/status epilepticus in rats". Chemico-Biological ... Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... See also: Receptor/signaling modulators • Muscarinic acetylcholine receptor modulators • Nicotinic acetylcholine receptor ...
Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... Aspartic acid (aspartate). *DIDS. *Direct blue 71. *Erythro-4-methyl-L-glutamic acid ... See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Metabotropic glutamate receptor modulators ... glutamate receptors, such as the NMDA receptor or the AMPA receptor, bind glutamate and are activated. Because of its role in ...
Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... Receptor/signaling modulators. GABA receptor modulators. GABAA receptor positive modulators. Ionotropic glutamate receptor ... Miller Jr, WT; Fager, EW; Griswold, PH (1948). "The Addition of Methyl Alcohol to Fluoroethylenes". Journal of the American ... See also: Receptor/signaling modulators • GABA receptor modulators • GABA metabolism/transport modulators ...
"Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5". ... "Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl D-aspartate antagonists". Neuroscience ... an antagonist to the NMDA receptor, which prevented LTP in this pathway.[24] Conversely, LTP in the mossy fiber pathway is NMDA ... AMPA receptors are the brain's most abundant glutamate receptors and mediate the majority of its excitatory activity. By ...
Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... Receptor/signaling modulators. GABA receptor modulators. GABAA receptor positive modulators. Ionotropic glutamate receptor ... Its molecule can be described as that of ethanol, with the three hydrogen atoms at position 2 (the methyl group) replaced by ... See also: Receptor/signaling modulators • GABA receptor modulators • GABA metabolism/transport modulators ...
GABAA receptor positive allosteric modulators. *AMPA receptor antagonists. *Glycine receptor agonists. *Kainate receptor ... Sodium thiopental is a member of the barbiturate class of drugs, which are relatively non-selective compounds that bind to an ... Sodium thiopental is mainly metabolized to pentobarbital,[29] 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid, and ... Receptor/signaling modulators. GABA receptor modulators. GABAA receptor positive modulators. Ionotropic glutamate receptor ...
GABA receptor agonists. *Glycine receptor agonists. *Biology of obsessive-compulsive disorder. *Peripherally selective drugs ... Antagonists/negative allosteric modulators: bicuculline, cicutoxin, flumazenil, furosemide, gabazine, oenanthotoxin, picrotoxin ... Activators: 3-Methyl-GABA. See also. Receptor/signaling modulators GABA receptor modulators GABAA receptor positive modulators ... Receptor/signaling modulators GABAA receptor positive modulators GABA metabolism/transport modulators ...
Traxoprodil (CP-101606); NR2A-selective antagonists: MPX-004. *MPX-007. *TCN-201 ... See also: Receptor/signaling modulators • GABA receptor modulators • GABA metabolism/transport modulators ... RS)-2-{[(aminocarbonyl)oxy]methyl}-2-methylpentyl isopropylcarbamate. CAS Number. *78-44-4 Y ...
NMDA receptor antagonist. References[edit]. *^ a b Jaiswal MK, Zech WD, Goos M, Leutbecher C, Ferri A, Zippelius A, Carrì MT, ... 2012). "Excitotoxic potential of the cyanotoxin β-methyl-amino-l-alanine (BMAA) in primary human neurons". Toxicon. 60 (6): ... Ischemia is followed by accumulation of glutamate and aspartate in the extracellular fluid, causing cell death, which is ... contributing to the selective vulnerability of MNs in ALS. Jaiswal et al., 2009.[1] ...
Conantokin G Is an NR2B-Selective Competitive Antagonist ofN-Methyl-d-aspartate Receptors. Sean D. Donevan and R. Tyler McCabe ... Conantokin G Is an NR2B-Selective Competitive Antagonist ofN-Methyl-d-aspartate Receptors. Sean D. Donevan and R. Tyler McCabe ... Conantokin G Is an NR2B-Selective Competitive Antagonist ofN-Methyl-d-aspartate Receptors. Sean D. Donevan and R. Tyler McCabe ... Conantokin G Is an NR2B-Selective Competitive Antagonist ofN-Methyl-d-aspartate Receptors ...
Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides. In: ... Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides. ... Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides. / ... T1 - Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides ...
... receptor antagonists reduce injury-induced pain behavior, but generally produce unacceptable side effects. In this study, we ... Subunit non-selective N-methyl-D-aspartate (NMDA) ... Subunit non-selective N-methyl-D-aspartate (NMDA) receptor ... Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and ... which are selective inhibitors of the NR2B or NR2A and NR2B subtypes of the NMDA receptor, respectively. We tested the effects ...
N-methyl-D-aspartate antagonists. The N-methyl-D-aspartate (NMDA) receptor antagonist esketamine intranasal (Spravato) has been ... Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med. 2006 Feb 9 ... It also modulates serotonin receptor activity through 5-HT1A receptor agonism and 5-HT3 receptor antagonism, although the ... Mirtazapine is a potent antagonist at 5-HT2, 5-HT3, alpha2-, and histamine (H1) receptors and, thus, can be very sedating and ...
"Conantokin G is an NR2B-selective competitive antagonist of N-methyl-D-aspartate receptors". Molecular Pharmacology. 58 (3): ... Conantokins act as potent and specific antagonists of the N-methyl-D-aspartate receptor (NMDAR).[1] They are the only naturally ... "Novel conantokins from Conus parius venom are specific antagonists of N-methyl-D-aspartate receptors". The Journal of ... a novel peptide antagonist to the N-methyl-D-aspartic acid (NMDA) receptor". Neuroscience Letters. 118 (2): 241-4. doi:10.1016/ ...
... an NR2B-selective N-methyl D-aspartate receptor antagonist, in subjects with acute ischemic stroke. Stroke 35: 241-241. *Web of ... Enantiomeric propanolamines as selective N-methyl-D-aspartate 2B receptor antagonists. J Med Chem 51: 5506-5521. *CrossRef, ... Structural basis of NR2B-selective antagonist recognition by N-methyl-D-aspartate receptors. Mol Pharmacol 75: 60-74. *CrossRef ... 4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N-methyl-D-aspartate antagonist. J Pharmacol Exp Ther 302: 940-948 ...
H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists.. Hansen ... H3 Receptor Antagonists Clobenpropit and Iodophenpropit as Subunit-Selective N-Methyl-d-Aspartate Receptor Antagonists ... H3 Receptor Antagonists Clobenpropit and Iodophenpropit as Subunit-Selective N-Methyl-d-Aspartate Receptor Antagonists ... H3 Receptor Antagonists Clobenpropit and Iodophenpropit as Subunit-Selective N-Methyl-d-Aspartate Receptor Antagonists ...
... selective N‐methyl‐D‐aspartate receptor antagonist". Pharmacology Research & Perspectives. 3 (6): e00198. doi:10.1002/prp2.198 ... to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP- ... Rislenemdaz is a small-molecule antagonist of the NMDA receptor. The NMDA receptor is composed of several subunits, but ... selective NMDA receptor subunit 2B (NR2B) antagonist which is under development by Cerecor in the United States as an ...
Non-competitive N-methyl-D-aspartate receptor antagonists.. Selective serotonin reuptake inhibitors ... Non-competitive N-methyl-D-aspartate receptor antagonists. Esketamine (Ketanest®, Spravato®) is a non-competitive N-methyl-D- ... aspartate receptor antagonist approved in 2019. This antidepressant is only available as a nasal spray and is to be used ...
2009b) Structural basis of NR2B-selective antagonist recognition by N-methyl-D-aspartate receptors. Mol Pharmacol 75:60-74. ... 2012) Mapping the binding of GluN2B-selective N-methyl-D-aspartate receptor negative allosteric modulators. Mol Pharmacol 82: ... 1997) Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. ... Preparation of imidazole derivatives as NMDA (N-methyl-D-aspartate) receptor subtype 2B selective blockers. Patent #WO ...
"Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5". ... "Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl D-aspartate antagonists". Neuroscience ... an antagonist to the NMDA receptor, which prevented LTP in this pathway.[24] Conversely, LTP in the mossy fiber pathway is NMDA ... AMPA receptors are the brains most abundant glutamate receptors and mediate the majority of its excitatory activity. By ...
The site of action is located at the extracellular vestibule of the receptors ion channel pore and is accessible after ... receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of ... N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity and their dysfunction is implicated in multiple brain ... 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex. ...
Conantokin G is an NR2B-selective competitive antagonist of N-methyl-D-aspartate receptors. Mol. Pharmacol. 58, 614-623 (2000). ... AMPA/kainate receptor antagonist)], bicuculline {10 μM; Tocris [γ-aminobutyric acid type A (GABAA) receptor antagonist]}, ... Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats. J. ... The upregulation of NR2A-containing N-methyl-d-aspartate receptor function by tyrosine phosphorylation of postsynapticdensity ...
... or a N-methyl-d-aspartate receptor antagonist (NMDAR: memantine) (42). Prevalence of NPS The prevalence of NPS was calculated ... Selective serotonin re-uptake inhibitors; AChEI: acetylcholinesterase inhibitor; NMDAR: N-methyl-d-aspartate receptor ... or a N-methyl-d-aspartate receptor antagonist (NMDAR: memantine) (42). Prevalence of NPS The prevalence of NPS was calculated ... N-methyl-d-aspartate receptor antagonist; MMSE: Mini-Mental State Examination; NPI: Neuropsychiatric Inventory. View Large ...
... but not to selective μ or δ agonists in mice. Pain 68:229-237. ... by the competitive N-methyl-D-aspartate receptor antagonist, ... Attenuation of μ-Opioid Tolerance and Cross-Tolerance by the Competitive N-Methyl-d-aspartate Receptor Antagonist LY235959 Is ... Attenuation of μ-Opioid Tolerance and Cross-Tolerance by the Competitive N-Methyl-d-aspartate Receptor Antagonist LY235959 Is ... Attenuation of μ-Opioid Tolerance and Cross-Tolerance by the Competitive N-Methyl-d-aspartate Receptor Antagonist LY235959 Is ...
7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex. ... burst elicited in CA3 hippocampal neurons by a variety of convulsants are not blocked by N-methyl-D-aspartate antagonists. ... Gaiarsa, J.L., Corradetti, R., Cherubini, E. and Ben-Ari, Y. (1990) The allosteric glycine site of the N-methyl-D-aspartate ... NMDA Receptor Pyramidal Neuron Excitatory Amino Acid Gaba Release Bath Application These keywords were added by machine and not ...
1988) 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor ... 1992) Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc ... Identification of selective NMDA receptor (NMDAR) antagonists (3) permitted ascribing its requirement (4) for the long-term ... 1981) 2-Amino-5-phosphonovalerate (2APV), a potent and selective antagonist of amino acid-induced and synaptic excitation. ...
Donevan SD, McCabe RT ( 2000) Conantokin G is an NR2B-selective competitive antagonist of N-methyl-d-aspartate receptors. Mol ... Luo J, Wang Y, Yasuda RP, Dunah AW, Wolfe BB ( 1997) The majority of N-methyl-d-aspartate receptor complexes in adult rat ... Blahos II J, Wenthold RJ ( 1996) Relationship between N-methyl-d-aspartate receptor NR1 splice variants and NR2 subunits. J ... Chazot PL, Coleman SK, Cik M, Stephenson FA ( 1994) Molecular characterization of N-methyl-d-aspartate receptors expressed in ...
This raises the question of how both NMDAR antagonists and agonists are able to have converging behavioral effects. Here we ... This raises the question of how both NMDAR antagonists and agonists are able to have converging behavioral effects. Here we ... However, studies showing that not all NMDAR antagonists are able to act as antidepressants challenge this notion. Furthermore, ... However, studies showing that not all NMDAR antagonists are able to act as antidepressants challenge this notion. Furthermore, ...
1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-d-aspartate receptor antagonist, ... 1989) Drug receptors and the inhibition of nerve cells. Br J Pharmacol 98:13-28. ... 1995) Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon1 subunit. Nature 373:151-155. ... 1994) Differential regulation by cAMP-dependent protein kinase and protein kinase C of the mu opioid receptor coupling to a G ...
It is a symptomatic approach based on the use of cholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists ... Receptor-mediated endocytosis (RME) provides a means for selective uptake of macromolecules. Cells have receptors for the ... Aspartate binds specifically to the NMDA glutamate receptor which is regulated both by a glutamate molecule and by voltage. ... Both GSH and (R)-α-lipoic acid (LA) get covalently linked with the NMDA receptor antagonists memantine (MEM) and are used in ...
... an agonist or antagonist of the 5-HT1AR, GABAARs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. The ... serotonin type1A receptor (5-HT1ARs) and the gamma-aminobutyric acid type A receptors (GABAARs). Several studies showed that ... an agonist or antagonist of the 5-HT1AR, GABAARs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. The ... serotonin type1A receptor (5-HT1ARs) and the gamma-aminobutyric acid type A receptors (GABAARs). Several studies showed that ...
These substances were recently reported to act as N‐methyl‐D‐aspartate (NMDA) antagonists. In the present study, we examined ... These findings indicate that conantokin‐G acts as a noncompetitive NMDA antagonist through an allosteric inhibition of ... The neurochemical profile of this polypeptide is distinct from previously described noncompetitive NMDA antagonists. ... Conantokin G Is an NR 2 B-Selective Competitive Antagonist of N-Methyl-D-aspartate Receptors ...
Traxoprodil (CP-101,606) is a potent noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, selective for the NR2B ... NR2B selective NMDA glutamate receptor antagonist which appears to target the "polyamine site" on the NMDA receptor, setting it ... ASTAR (Antagonist of Serotonin 5HT2A Receptors). SR-46349 is an antagonist of 5-HT (2A/2C) receptor and increases the release ... It is more that 5-fold selective for mu opioid receptor compared to kappa opioid receptors and 13-fold selective over delta ...
7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex. ... while kynurenine acid is its neuroprotective metabolite and an antagonist of the N-methyl-D-aspartate (NMDA) receptor [9,10]. ... Kessler, M.; Terramani, T.; Lynch, G.; Baudry, M. A glycine site associated with N-methyl-D-aspartic acid receptors: ... An endogenous antagonist of excitatory amino acid receptors. J. Neurosci. 1990, 10, 2965-2973. [Google Scholar] [CrossRef] ...
Although antagonists to GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) have been widely considered to be ... receptors in cognitive deficits in DS by defining the effect of selective GABA(B) receptor antagonists on behavior and synaptic ... Regional levels of tyrosine phosphorylation of proteins in general and the N-methyl-D-aspartate receptor subunit NR2 in ... Both a calcineurin inhibitor, FK506, and a selective NMDA receptor antagonist, MK-801, inhibit the dephosphorylation of DAPK ...
... and NR2D-selective NMDA receptor antagonists and that residues A414 and T428 may determine subunit variations in agonist ... Identification of Subunit- and Antagonist-Specific Amino Acid Residues in the N-Methyl-d-aspartate Receptor Glutamate-Binding ... Identification of Subunit- and Antagonist-Specific Amino Acid Residues in the N-Methyl-d-aspartate Receptor Glutamate-Binding ... Identification of Subunit- and Antagonist-Specific Amino Acid Residues in the N-Methyl-d-aspartate Receptor Glutamate-Binding ...
Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. ... DNQX and AP3 are selective antagonists of glutamate NMDA (N-methyl-D-aspartate), AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole ... amnesic influence of the N-methyl-D-aspartate (NMDA) glutamate receptor blocker, 2-amino-5-phosphono pentanoic acid (AP5) ( ... Memory consolidation induces N-methyl- D-aspartic acid-receptor- and Ca2+/ calmodulin-dependent protein kinase II-dependent ...
The EPSCs were pharmacologically isolated into their non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor-mediated components ... by using selective antagonists. The effects of halothane on EPSC amplitude and kinetics were analyzed at various membrane ... Effects of halothane on glutamate receptor-mediated excitatory postsynaptic currents. A patch-clamp study in adult mouse ... Halothane depresses glutamatergic EPSCs irrespective of receptor subtype, most likely by inhibition of glutamate release. ...
Like its cousin, phencyclidine, ketamine is a selective and potent N-methyl-d-aspartate (NMDA) receptor antagonist. It is ... A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63: ... Zarate and his colleagues have found that the NMDA receptor antagonist memantine (Namenda) doesnt relieve depression and that ... Among that evidence are data that clearly implicate NMDA, a glutamate receptor, in the action of antidepressants: NMDA receptor ...
  • Conantokin G (Con G) is a 17-amino-acid peptide antagonist of N -methyl- d -aspartate (NMDA) receptors isolated from the venom of the marine cone snail, Conus geographus . (aspetjournals.org)
  • In this study the mechanism of action and subunit selectivity of Con G was examined in whole-cell voltage-clamp recordings from cultured neurons and in two electrode voltage-clamp recordings from Xenopus oocytes expressing recombinant NMDA receptors. (aspetjournals.org)
  • Con G was a potent and selective antagonist of NMDA-evoked currents in murine cortical neurons (IC 50 = 480 nM). (aspetjournals.org)
  • The slow onset of Con G block could be prevented by coapplication with high concentrations of NMDA or of the competitive antagonist ( RS )-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid. (aspetjournals.org)
  • Furthermore, in oocytes expressing NR1a/NR2B receptors, Con G produced a rightward shift in the concentration-response curve for NMDA, providing support for a competitive interaction with the NMDA-binding site. (aspetjournals.org)
  • Finally, Con G selectively blocked NMDA receptors containing the NR2B subunit. (aspetjournals.org)
  • These results demonstrate that Con G is a subunit-specific competitive antagonist of NMDA receptors. (aspetjournals.org)
  • The unique subunit selectivity profile of Con G may explain its favorable in vivo profile compared with nonselective NMDA antagonists. (aspetjournals.org)
  • 4-Benzylpiperidine-1-yl)-(6-hydroxy-1H-indole-2-yl)-methanone (6a) derived from (E)-1 -(4-benzylpiperidin-1-yl)-3-(4-hydroxy-phenyl)-propenone (5) was identified as a potent NR2B subunit-selective antagonist of the NMDA receptor. (elsevier.com)
  • Subunit non-selective N-methyl-D-aspartate (NMDA) receptor antagonists reduce injury-induced pain behavior, but generally produce unacceptable side effects. (nih.gov)
  • In this study, we examined the antinociceptive and motor effects of cone snail venom-derived peptides, conantokins G and T (conG and conT), which are selective inhibitors of the NR2B or NR2A and NR2B subtypes of the NMDA receptor, respectively. (nih.gov)
  • The study supports the notion that drugs directed against subtypes of the NMDA receptor, by virtue of their reduced side-effect profile, hold promise as novel therapeutic agents for the control of pain. (nih.gov)
  • N-Methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that mediate a slow, Ca(2+)-permeable component of excitatory synaptic transmission in the central nervous system and play a pivotal role in synaptic plasticity, neuronal development, and several neurological diseases. (nih.gov)
  • We describe a fluorescence-based assay that measures NMDA receptor-mediated changes in intracellular calcium in a BHK-21 cell line stably expressing NMDA receptor NR2D with NR1 under the control of a tetracycline-inducible promoter (Tet-On). (nih.gov)
  • The assay is validated by successfully identifying known noncompetitive, but not competitive NMDA receptor antagonists among 1800 screened compounds from two small focused libraries, including the commercially available library of pharmacologically active compounds. (nih.gov)
  • Hits from the primary screen are validated through a secondary screen that used two-electrode voltage-clamp recordings on recombinant NMDA receptors expressed in Xenopus laevis oocytes. (nih.gov)
  • This strategy identified several novel modulators of NMDA receptor function, including the histamine H3 receptor antagonists clobenpropit and iodophenpropit, as well as the vanilloid receptor transient receptor potential cation channel, subfamily V, member 1 (TRPV1) antagonist capsazepine. (nih.gov)
  • These compounds are noncompetitive antagonists and the histamine H3 receptor ligand showed submicromolar potency at NR1/NR2B NMDA receptors, which raises the possibility that compounds can be developed that act with high potency on both glutamate and histamine receptor systems simultaneously. (nih.gov)
  • Furthermore, it is possible that some actions attributed to histamine H3 receptor inhibition in vivo may also involve NMDA receptor antagonism. (nih.gov)
  • Rislenemdaz (developmental code names CERC-301, MK-0657) is an orally-active, selective NMDA receptor subunit 2B (NR2B) antagonist which is under development by Cerecor in the United States as an adjunctive therapy for treatment-resistant depression (TRD). (wikipedia.org)
  • Rislenemdaz is a small-molecule antagonist of the NMDA receptor. (wikipedia.org)
  • The NMDA receptor is composed of several subunits, but rislenemdaz is specific for the GluN2B subunits which are only seen in the spinal cord and forebrain. (wikipedia.org)
  • Cerecor acquired the exclusive rights from Merck in 2013 to develop an NMDA receptor antagonist for the treatment of major depressive disorder (MDD). (wikipedia.org)
  • This synaptic localization of PYK2, in turn, promoted the formation and synaptic integration of GluN2B-containing NMDA receptors, which is important for the synaptic plasticity that underlies learning and memory formation. (sciencemag.org)
  • BDNF induced the synaptic accumulation of GluN2B-containing NMDA receptors (NMDARs) and increased the amplitude of NMDAR-mediated miniature excitatory postsynaptic currents (mEPSCs) in cultured rat hippocampal neurons by a mechanism requiring activation of the protein tyrosine kinase Pyk2 and dependent on cellular protein synthesis. (sciencemag.org)
  • Although NMDA receptor antagonists attenuate the development of morphine tolerance, it is not clear whether NMDA receptor antagonists also prevent tolerance and cross-tolerance to other μ-opioid agonists and, if so, whether prevention is related to the efficacy of the agonist used to examine tolerance. (aspetjournals.org)
  • A rat tail-withdrawal procedure was used to test the antinociceptive effects of the μ-opioids etorphine, morphine, and dezocine before and after twice-daily subcutaneous injections with either 0.003 mg/kg etorphine, 10 mg/kg morphine, or 3.0 mg/kg dezocine, each administered alone or in combination with 3.0 mg/kg of the competitive NMDA antagonist LY235959. (aspetjournals.org)
  • Recently, we reported that the maintenance dose of morphine is related to the magnitude of morphine tolerance and the attenuation of that tolerance with an NMDA receptor antagonist ( Allen and Dykstra, 2000 ). (aspetjournals.org)
  • Thus, differences in the efficacy of an opioid agonist represent a parameter that may determine the effectiveness of an NMDA receptor antagonist to attenuate tolerance. (aspetjournals.org)
  • These differences may represent another variable that determines the extent to which an NMDA receptor antagonist modulates opioid tolerance. (aspetjournals.org)
  • The purpose of this study was to determine the role of the competitive NMDA receptor antagonist LY235959 in the attenuation of tolerance and cross-tolerance to μ-opioid agonists with different efficacies. (aspetjournals.org)
  • NMDA receptors-their role in long-term potentiation. (springer.com)
  • NMDA receptor (NMDAR) activation controls long-term potentiation (LTP) as well as long-term depression (LTD) of synaptic transmission, cellular models of learning and memory. (pnas.org)
  • Glutamate, the major excitatory transmitter in the brain, acts on several receptors that have been divided into ionotropic [(AMPA, NMDA, kainate) those whose primary function is to allow entry of ions into neurons] and metabotropic [(mGluR1-8) those that through conformational changes drive intracellular signaling pathways independent of ion-channel flow] classes ( 1 , 2 ). (pnas.org)
  • Identification of selective NMDA receptor (NMDAR) antagonists ( 3 ) permitted ascribing its requirement ( 4 ) for the long-term potentiation (LTP) of synaptic transmission triggered by a high-frequency stimulus ( 5 ). (pnas.org)
  • NMDA receptors (NMDARs) are essential for modulating synaptic strength at central synapses. (jneurosci.org)
  • Here we investigated the role of these NMDA receptor subtypes in long-term potentiation (LTP) induction. (jneurosci.org)
  • These substances were recently reported to act as N‐methyl‐D‐aspartate (NMDA) antagonists. (semanticscholar.org)
  • The resolved X-ray crystal structures of the glutamate-binding domain (S1/S2 domains) of the GluR2 and NR1 glutamate receptor subunits were used to model the homologous regions of the N -methyl- d -aspartate (NMDA) receptor's NR2 subunits. (aspetjournals.org)
  • Consistent with these predictions, cis -PPDA displays a 35-fold higher affinity for NR2B-containing NMDA receptors than trans -PPDA. (aspetjournals.org)
  • Of these residues, mutational analysis and modeling suggest that A414, R712, and G713 (NR2B numbering) may be especially useful for developing NR2C- and NR2D-selective NMDA receptor antagonists and that residues A414 and T428 may determine subunit variations in agonist affinity. (aspetjournals.org)
  • The EPSCs were pharmacologically isolated into their non-N-methyl-D-aspartate (non-NMDA) and NMDA receptor-mediated components by using selective antagonists. (nih.gov)
  • Like its cousin, phencyclidine, ketamine is a selective and potent N -methyl-d-aspartate (NMDA) receptor antagonist. (psychiatrictimes.com)
  • Now an adjunct assistant clinical professor of psychiatry at Yale University in New Haven, Connecticut, Berman suspects that the scientific community may be more open to the idea that an NMDA receptor antagonist could be an antidepressant. (psychiatrictimes.com)
  • and, antidepressants alter the expression of messenger RNA that encodes NMDA receptor subunits. (psychiatrictimes.com)
  • Thiokynurenates: a new group of antagonists of the glycine modulatory site of the NMDA receptor. (abcam.com)
  • DESPITE extensive experimental and clinical literature related to the analgesic properties of the clinically available N -methyl-d-aspartate (NMDA) receptor antagonists on somatic nociception, relatively few studies have been performed on the analgesic effect of ketamine in models of visceral pain. (asahq.org)
  • 7 A direct inhibitory effect on these responses was observed when ketamine was administered intravenously and intrathecally, with a similar effect as two other clinically available NMDA receptor antagonists, memantine and dextromethorphan. (asahq.org)
  • A spinally mediated NMDA receptor antagonist effect was thereby suggested. (asahq.org)
  • The effects of two other clinically available NMDA receptor antagonists, dextromethorphan and memantine, on these responses to UBD were also examined. (asahq.org)
  • Bormann J (1989) Nemantine is a potent blocker of N-methyl- d -aspartate (NMDA) receptor channels. (springer.com)
  • In the absence of added Mg2+, N-methyl-D-aspartate (NMDA)-receptor antagonists depressed the release of glutamate, aspartate, and gamma-aminobutyrate evoked by 50 mM K+. (nih.gov)
  • Conversely, the agonist NMDA selectively enhanced the release of aspartate. (nih.gov)
  • These results suggest that the activation of NMDA receptors by endogenous glutamate and aspartate enhances the subsequent release of these amino acids. (nih.gov)
  • The cellular mechanism may involve Ca2+ influx through presynaptic NMDA receptor channels or liberation of a diffusible neuromodulator linked to the activation of postsynaptic NMDA receptors. (nih.gov)
  • 7-Hlorokinurenska kiselina (7-CTKA) je antagonist NMDA receptora sa antidepresantskim dejstvom na pacovima. (wikipedia.org)
  • NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission in the brain. (eurekamag.com)
  • Subunit-selective antagonists that discriminate between the glycine sites of GluN1 and GluN3 subunits would be valuable pharmacological tools for studies on the function and physiological roles of NMDA receptor subtypes. (eurekamag.com)
  • In addition, TK40 displayed >100-fold selectivity for GluN1/N2 NMDA receptors over GluN3A- and GluN3B-containing NMDA receptors and no appreciable effects at AMPA receptors. (eurekamag.com)
  • Ichitani, Yukio 2015-10-22 00:00:00 The possible involvement of hippocampal N-methyl-d-aspartate (NMDA) receptors in spontaneous object recognition was investigated in rats under different memory load conditions. (deepdyve.com)
  • These results suggest that hippocampal NMDA receptors play a critical role in spontaneous object recognition only when the memory load is high. (deepdyve.com)
  • It did not attract scientists' attention until the 1980s and 1990s when it was found that KYNA is an antagonist of ionotropic glutamate receptors, including N-methyl-D-aspartate (NMDA), α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate receptors [ 2 - 6 ]. (hindawi.com)
  • NO is synthesized from L-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino acids. (biopsychiatry.com)
  • NMDA receptor antagonists also produce antidepressant-like actions in preclinical models. (biopsychiatry.com)
  • In summery I will try and piece together this theory that certain drugs act primarily as NMDA antagonists. (drugs-forum.com)
  • This is a good model of action of Dissociative drugs and is commonly used as the basis for current NMDA receptor study. (drugs-forum.com)
  • Potent, selective and competitive NMDA antagonist (K i = 310 nM for inhibition of [ 3 H]-CPP binding in rat brain). (tocris.com)
  • D'Hooge et al (1999) Effects of competitive NMDA receptor antagonists on excitatory amino-acid-evoked currents in mouse spinal cord. (tocris.com)
  • N-methyl-D-aspartate (NMDA) receptor antagonists have been reported to inhibit morphine analgesic tolerance in many studies. (jove.com)
  • modulated NMDA receptor trafficking in a rat model of remifentanil-induced postoperative hyperalgesia. (jove.com)
  • activity as well as NMDA receptor subunits (NR1, NR2A and NR2B) expression and trafficking in spinal cord L4-L5 segments were measured by Western blot analysis. (jove.com)
  • We found that remifentanil infusion at 1 ?g·kg(-1)·min(-1) and 2 ?g·kg(-1)·min(-1) caused mechanical and thermal hyperalgesia, up-regulated NMDA receptor subunits NR1 and NR2B expression in both membrane fraction and total lysate of the spinal cord dorsal horn and increased GSK-3? (jove.com)
  • Furthermore, remifentanil incubation increased amplitude and frequency of NMDA receptor-induced current in dorsal horn neurons, which was prevented with the application of TDZD-8. (jove.com)
  • can significantly ameliorate remifentanil-induced hyperalgesia via modulating the expression and function of NMDA receptors, which present useful insights into the mechanistic action of GSK-3? (jove.com)
  • Although detailed molecular mechanisms have yet to be established, studies investigating TRPV1-dependent nociception or hyperalgesia have demonstrated that the activation of TRPV1 receptors increased the miniature excitatory postsynaptic potentials in a brain slice obtained from the dorsolateral periaqueductal gray neuron through the selective potentiation of glutamatergic N -methyl- d -aspartate (NMDA) neurotransmission ( 77 ). (physiology.org)
  • When comparing TRPV1 knockout animals with wild-type mice characterized by a postinflammatory hyperalgesia that was reversed by the NMDA antagonist ( 54 ), it was found that the TRPV1-dependent modulation on NMDA neurotransmission may underlie the enhancement of pain signaling in the central nervous system and therefore elicits postinjury or postinflammation ( 12 , 21 , 45 , 62 , 63 , 74 , 75 ). (physiology.org)
  • Recently, phosphorylation of tyrosine residues in the NR2 subunit of NMDA receptors, which defines the properties essential for spinal neural plasticity, has been shown to be an important determinant for the induction of NMDA-dependent postinflammatory hyperalgesia ( 13 , 27 ). (physiology.org)
  • Hippocampal dependent learning ability correlates with N-methyl-D-aspartate (NMDA) receptor levels in CA3 neurons of young and aged rats. (pubmedcentralcanada.ca)
  • In the presence of glutamate and postsynaptic depolarization, N -methyl- d -aspartate (NMDA)-type receptors allow Ca 2+ to enter the neuron. (physiology.org)
  • Background and Purpose -Aptiganel (CNS 1102) is a selective, noncompetitive antagonist that acts on the ion channel associated with the N -methyl- d -aspartate (NMDA) receptor and is neuroprotective in experimental focal cerebral ischemia models at a plasma concentration of 10 ng/mL. (ahajournals.org)
  • 1 Aptiganel [ N -(1-naphthyl)- N -(3-ethyl phenyl)- N -methyl guanidine hydrochloride (CNS 1102)] is a selective noncompetitive antagonist within the ion-channel pore of the N -methyl- d -aspartate (NMDA) receptor. (ahajournals.org)
  • The deleterious effects from excitotoxicity result from calcium entry through a specific glutamate receptor, the N-methyl D-aspartate (NMDA) receptor. (upenn.edu)
  • NMDA receptor antagonists act both as neuroprotective agents against excitotoxicity and as anticonvulsants in animals, but human clinical trials with the most potent agents have been complicated by side effects including psychosis. (upenn.edu)
  • Much evidence indicates the presence of multiple types of NMDA receptors in the brain, and evidence from our laboratory suggests that different subtypes play different roles in physiological and excitotoxic processes. (upenn.edu)
  • If one could develop therapeutic agents which are selective for the subtypes involved in excitotoxicity, one could more readily utilize NMDA receptor antagonists for treatment of human diseases. (upenn.edu)
  • We use a systematic approach to examine the subtype specific physiological and pharmacological properties of NMDA receptors. (upenn.edu)
  • NMDA receptors are created in tissue culture expression systems, and their properties are studied biochemically, pharmacologically and physiologically to correlate receptor properties in these systems with such properties in vivo. (upenn.edu)
  • We have previously shown that different NMDA receptor subtypes have distinct pharmacologies and produce different changes in intracellular calcium. (upenn.edu)
  • Combined with our studies on the pharmacological specificity of NMDA receptor subtypes, this will facilitate the development of therapeutic agents directed to those NMDA receptors which play crucial roles in excitotoxicity. (upenn.edu)
  • Bielenberg GW (1989): Pre-or postischemic treatment with NMDA antagonists reduces infarct size after MCA occlusion in rat. (springer.com)
  • Buchan AM (1990): Do NMDA antagonists protect against cerebral ischemia: Are clinical trials warranted? (springer.com)
  • Bullock R, Graham DI, Chen M-H, Lowe D, McCulloch J (1990): Focal cerebral ischemia in the cat: Pretreatment with a competitive NMDA receptor antagonist, D-CPP-ene. (springer.com)
  • Zhou et al (1999) 4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: a novel, potent, and selective NR1/2B NMDA receptor antagonist. (tocris.com)
  • Higgins et al (2003) Evaluation of the NR2B-selective NMDA receptor antagonist Ro 63-1908 on rodent behaviour: evidence for an involvement of NR2B NMDA receptors in response inhibition. (tocris.com)
  • Quillinan et al (2015) Region-specific role for GluN2B-containing NMDA receptors in injury to Purkinje cells and CA1 neurons following global cerebral ischemia. (tocris.com)
  • Recent preclinical studies have shown that enhancing NMDA receptor (NMDAR) activity can exert rapid antidepressant-like effects. (nature.com)
  • Capturing the angel in "angel dust": twenty years of translational neuroscience studies of NMDA receptor antagonists in animals and humans. (nature.com)
  • [3,4] Transient reduction of GABA A receptor-mediated inhibitory postsynaptic currents (IP-SCs) is thought to play a role in regulating N-methyl-D-aspartate (NMDA) receptor-dependent mechanisms of synaptic plasticity. (asahq.org)
  • [3,4] The resulting depolarization can recruit previously inactive receptors, for example, by relieving the magnesium-voltage-dependent block of the NMDA receptor-mediated calcium channel. (asahq.org)
  • [3,4] Prolongation of the open-time of the GABA A receptor-chloride channel by pentobarbital [2,11] partially depolarizes the postsynaptic membrane, enhancing conductance at the NMDA receptor-mediated calcium channel. (asahq.org)
  • NMDA (N-methyl-D-aspartate) is the selective agonist that binds to NMDA receptors but not to other glutamate receptors. (pinterest.com)
  • The NMDA receptor (NMDAR) is the predominant molecular device for controlling synaptic plasticity and memory function. (pinterest.com)
  • Activation of NMDA receptors requires binding of glutamate or aspartate (aspartate does not stimulate the receptors as strongly). (pinterest.com)
  • E7023 SIGMA-ALDRICH Ethyl alcohol, Pure 200 proof, for molecular biology _ http://www.sigmaaldrich.com/catalog/product/sigald/e7023?lang=en®ion=US _ Positive allosteric modulator of GABAA receptors, and negative allosteric modulator of NMDA glutamate receptors. (pinterest.com)
  • Antibody - Mouse Monoclonal antibody to Glutamate receptor ionotropic NMDA Reactivity: Human, Mouse, Rat. (pinterest.com)
  • CGS-19755, a competitive NMDA receptor antagonist, reduces calcium-calmodulin binding and improves outcome after global cerebral ischemia. (semanticscholar.org)
  • The competitive N-methyl-D-aspartate (NMDA) antagonist CGS 19755 attenuates the rate-decreasing effects of NMDA in rhesus monkeys without producing ketamine-like discriminative stimulus effects. (semanticscholar.org)
  • N-Methyl-D-aspartate (NMDA) antagonists reduce ischemic brain damage and associated hypermotility. (semanticscholar.org)
  • There is an urgent need, therefore, to identify well-tolerated, orally available compounds that target the NMDA receptor as a novel treatment approach for TRD. (clinicaltrials.gov)
  • The current project aims to test the safety, tolerability and efficacy of Nuedexta - containing the NMDA antagonist dextromethorphan. (clinicaltrials.gov)
  • Ketamine - a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist - has now been demonstrated in several studies to bring about a rapid and robust antidepressant effect, even in patients suffering from TRD. (clinicaltrials.gov)
  • The tinnitus research literature suggests that NMDA receptor antagonists may prove to be useful in reducing tinnitus. (clinicaltrials.gov)
  • Nitrous oxide, a member of the NMDA receptor antagonist class, is a widely-used general anesthetic and sedative with a proven safety profile. (clinicaltrials.gov)
  • The investigators hypothesized that the administration of nitrous oxide, an NMDA receptor antagonist, may be effective in treatment of tinnitus. (clinicaltrials.gov)
  • Nitrous oxide is an N-methyl-D-aspartate (NMDA) receptor antagonist, a class of drugs shown to have antidepressant effects. (clinicaltrials.gov)
  • Generally, NMDA receptors promote excitation at synapses throughout the auditory pathway and play diverse roles in synaptic development and auditory information processing. (clinicaltrials.gov)
  • In the setting of chronic damage to the auditory system, overactivation of NMDA receptors leads to aberrant spontaneous neuronal firing in the cochlea and auditory brainstem structures, which can further perpetuate damage and disease in a feed-forward mechanism. (clinicaltrials.gov)
  • showed that administration of NMDA receptor antagonists prior to the administration of salicylate was effective in preventing acute excitotoxic tinnitus, establishing that salicylate induces tinnitus through its action on NMDA receptors. (clinicaltrials.gov)
  • Thus, NMDA receptors are thought to be implicated in the generation and perpetuation of several auditory diseases including tinnitus. (clinicaltrials.gov)
  • Magnesium is also an adjuvant drug which has a key role in nociceptive transmission, and acts as a NMDA (N-Methyl-D-Aspartate) antagonist in spinal neurons. (clinicaltrials.gov)
  • The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. (biomedcentral.com)
  • N -methyl- D aspartate (NMDA) receptors are a class of glutamate receptors composed of heteromeric complexes containing an essential Grin1 subunit and an additional Grin2A - D or Grin3A - B subunit [ 1 - 3 ]. (biomedcentral.com)
  • The NMDA receptor (NMDAR) and the complex of proteins surrounding the receptor are susceptible to age-related changes in expression. (eneuro.org)
  • We found an age-related increase in the percentage of NMDA receptor-associated proteins that were palmitoylated in the frontal cortex of mice, which were associated with age-related deficits in memory and executive functions. (eneuro.org)
  • After crossing the blood-brain barrier and reaching brain astrocytes, AV-101 is rapidly and enzymatically converted into 7-chlorokynurenic acid (7-Cl-KYNA), a well-characterized, potent and selective antagonist of N-methyl-D-aspartate (NMDA) receptors, acting by blocking the glycine-binding co-agonist site of the NMDA receptor. (vistagen.com)
  • Electrophysiological evidence for the presence of NMDA receptors in the guinea pig cochlea. (neuroreille.com)
  • The compounds are ligands for the NR2B NMDA receptor and may be useful for the treatment of various disorders of the central nervous system. (sumobrain.com)
  • QBP, glutamine-binding protein Molecular architecture of NMDA receptors of NR1 and NR2 subunits forming a tetrameric complex oftwo NR1 and two NR2 subunits. (gotomydoctor.com)
  • It is also an antagonist of N-methyl-D-aspartate (NMDA) receptors. (omnicalab.com)
  • Dehydroepiandrosterone rapidly increases free intracellular calcium via activation of N-methyl-D-aspartate (NMDA) receptors. (selleckchem.com)
  • Adult male Wistar rats were treated before conditioned fear with FfB, vehicle, an agonist or antagonist of the 5-HT 1A R, GABA A Rs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. (frontiersin.org)
  • R )-Butaprost is a selective EP 2 prostanoid receptor agonist. (sigmaaldrich.com)
  • Metabolite of the chemotherapeutic drug tamoxifen, exhibiting more potent estrogen agonist/antagonist activity than the parent drug. (sigmaaldrich.com)
  • Linaclotide is an agonist of the guanylate cyclase type-C receptor found in the intestine and acts by a mechanism distinct from previously developed products for IBS-C and CC. Linaclotide is administered orally but acts locally in the intestine with no measurable systemic exposure. (fiercebiotech.com)
  • Linaclotide is an agonist of guanylate cyclase type-C, a receptor found on the lining of the intestine. (fiercebiotech.com)
  • RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, a selective quisqualate receptor agonist, and kainate, an agonist active at both kainate and quisqualate receptors, selectively depressed the K(+)-evoked release of aspartate. (nih.gov)
  • D-serine, the D-stereoisomer of serine, synthesized in the brain by serine racemase from its L-stereoisomer is considered a co-agonist I co-activator of glutamatergic N-methyl-0-aspartate receptors (NMDARs). (fsu.edu)
  • Kainate receptors containing the GluR5 subunit seemed to mediate the observed effect because a selective GluR5-containing kainate receptor antagonist blocked the changes in sIPSCs induced by Ca 2+ uncaging, and bath application of a selective GluR5-containing receptor agonist robustly potentiated sIPSCs. (pnas.org)
  • Additionally, it was indicated that KYNA is an agonist of GPR35 receptors which are mainly present in the gastrointestinal tract [ 21 ]. (hindawi.com)
  • We studied the effect of treatment with a cannabinoid receptor agonist on disease progression and life span in SODG93A mice. (420magazine.com)
  • MAIN METHODS: Rats were randomly assigned into three groups for intraperitoneal treatment with saline (CTL group), BD1047 (an antagonist of the S1R, BD group) or BD1047 plus fluvoxamine (an agonist of the S1R, BDâ ¯+â ¯F group) for 4â ¯weeks. (bvsalud.org)
  • In the present study, we have used an electrophysiological approach to investigate at this level the presence of a major type of excitatory amino acid receptor, namely the glutamatergic receptor for which N-methyl-D-aspartate is a selective agonist. (neuroreille.com)
  • Phenylephrine HCl is a selective α1 agonist. (omnicalab.com)
  • Dehydroepiandrosterone is an important endogenous steroid hormone, which is an androgen receptor antagonist and an estrogen receptor agonist. (selleckchem.com)
  • Gamma-hydroxybutyrate (GHB) is a GHB-/GABA-B receptor agonist inducing a broad spectrum of subjective effects including euphoria, disinhibition, and enhanced vitality. (readbyqxmd.com)
  • Conantokins act as potent and specific antagonists of the N-methyl-D-aspartate receptor (NMDAR). (wikipedia.org)
  • Because numerous pathologic conditions involve NMDAR overactivation, subunit-selective antagonists hold strong therapeutic potential, although clinical successes remain limited. (aspetjournals.org)
  • Among the most promising NMDAR-targeting drugs are allosteric inhibitors of GluN2B-containing receptors. (aspetjournals.org)
  • Kinetic, pharmacological and optical experiments showed that the steroid inhibition was not typical for a drug-receptor interaction in an aqueous solution compatible with the hypothesis that steroid accumulation in the plasma membrane is the route by which it accesses a binding site on the NMDAR 12 . (nature.com)
  • This finding is also supported by gene-targeted mutant mice expressing C-terminally truncated NR2A subunits, which participate in synaptic NMDAR channel formation and Ca 2+ signaling, as indicated by immunopurified synaptic receptors, postembedding immunogold labeling, and spinous Ca 2+ transients in the presence of NR2B blockers. (jneurosci.org)
  • Since the discovery that a single dose of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, had rapid and long-lasting antidepressant effects, there has been increased interest in using NMDAR modulators in the pharmacotherapy of depression. (frontiersin.org)
  • However, studies showing that not all NMDAR antagonists are able to act as antidepressants challenge this notion. (frontiersin.org)
  • This raises the question of how both NMDAR antagonists and agonists are able to have converging behavioral effects. (frontiersin.org)
  • Here we critically review the evidence and proposed therapeutic mechanisms for both NMDAR antagonists and agonists, and collate several theories on how both activation and inhibition of NMDARs appear to have antidepressant effects. (frontiersin.org)
  • However, recent attention has focused on the NMDAR as a therapeutic target for major depression, and despite often ambiguous mechanistic insight, both inhibition and stimulation of this receptor convey antidepressant properties. (frontiersin.org)
  • This review article will critically evaluate the current literature reporting the validity of NMDAR modulation in major depression, and will propose a mechanism by which the function of this receptor in an "on" or "off" state may have antidepressant actions. (frontiersin.org)
  • The NMDAR is a type of ionotropic glutamate receptor. (pinterest.com)
  • The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. (ox.ac.uk)
  • N-methyl-D-aspartate receptor (NMDAR) antagonists have been found to be effective to inhibit morphine dependence. (bvsalud.org)
  • However, the discovery of the selective antagonist for NMDAR GluN2B with low side-effects still remains challenging. (bvsalud.org)
  • In the present study, we report a selective NMDAR GluN2B antagonist con-T[M8Q](a conantokin-T variant) that potently inhibits the naloxone-induced jumping and conditioned place preference of morphine-dependent mice at nmol/kg level, 100-fold higher than ifenprodil, a classical NMDAR NR2B antagonist. (bvsalud.org)
  • Moreover, NR2B-containing receptors, compared with other NMDAR subtypes, appear to contribute preferentially to pathological processes linked to overexcitation of glutamatergic pathways. (gotomydoctor.com)
  • N -methyl- d -aspartate receptors (NMDARs) are glutamate-gated ion channels that play key roles in brain physiology and pathology. (aspetjournals.org)
  • These data widen the allosteric and pharmacological landscape of NMDARs and offer a renewed structural framework for designing next-generation GluN2B antagonists with therapeutic value for brain disorders. (aspetjournals.org)
  • N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity and their dysfunction is implicated in multiple brain disorders. (nature.com)
  • A major question arose after the finding that a low-frequency stimulus (LFS) produced long-term depression (LTD) of synaptic transmission that was also blocked by an antagonist to NMDARs ( 9 , 10 ). (pnas.org)
  • The N-methyl-D-aspartate receptors (NMDARs) are a class of ionotropic glutamate receptors that are widely expressed in the brain. (frontiersin.org)
  • the major targets of these substances are N-methyl-D-aspartic acid receptor (NMDARs), serotonin type1A receptor (5-HT 1A Rs), and the gamma-aminobutyric acid type A receptors (GABA A Rs). (frontiersin.org)
  • We have determined that D-serine works as a potent antagonist I inhibitor of GluN3-containing triheteromeric NMDARs that were discovered in our laboratory recently and found to exist in various regions of the brain. (fsu.edu)
  • 3. D-serine's antagonism of GluN3-containing triheteromeric NMDARs may be important because these receptors appear significantly more permeable 1 selective for calcium, a potent excitotoxicant that underlies cell death under a number of scenarios including epilepsy. (fsu.edu)
  • In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(A)Rs). (ox.ac.uk)
  • Interestingly, NMDARs are endowed with multiple extracellular regulatory sites that recognize ions or small molecule ligands, some of which are likely to regulate receptor function in vivo . (gotomydoctor.com)
  • Burnashev N, Monyer H, Seeburg PH, Sakmann B (1992) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. (springer.com)
  • This effect was blocked by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptor antagonists, but not by selective AMPA receptor or N -methyl- d -aspartate receptor antagonists. (pnas.org)
  • When tetrodotoxin was included to block action potentials, Ca 2+ uncaging induced a small decrease in the frequency of miniature inhibitory postsynaptic currents, which was not affected by AMPA/kainate receptor antagonists. (pnas.org)
  • By combining Herpes virus-mediated in vivo gene delivery with in vitro patch-clamp recordings, I reported contextual learning drives GluR1-containing AMPA receptors into CA3-CA1 synapses. (aimspress.com)
  • IA training induced ACh release in CA1 that strengthened not only AMPA receptor-mediated excitatory synapses, but also GABA A receptor-mediated inhibitory synapses on each CA1 neuron. (aimspress.com)
  • 2011) Contextual learning requires synaptic AMPA receptor delivery in the hippocampus. (aimspress.com)
  • Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl D-aspartate antagonists. (pubmedcentralcanada.ca)
  • 1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. (aimspress.com)
  • 11. Auerbach JM, Segal M (1996) Muscarinic receptors mediating depression and long-term potentiation in rat hippocampus. (aimspress.com)
  • It is generally assumed that the synaptic inhibition in adult hippocampus is mediated by GABA, which acts on GABA-A (Ben-Ari and al 1981, Alger and Nicoll 1982, Kehl and Mc Lennan 1985), and GABA-B receptors, coupled to chloride and potassium channels respectively (Alger-and Nicoll 1982, Dutar and Nicoll 1988). (springer.com)
  • When the inhibition is blocked by GABAergic antagonist, interictal discharges, mediated by excitatory amino acids appear (Wong and Traub 1983, Neuman and al 1988 b). (springer.com)
  • Halothane depresses glutamatergic EPSCs irrespective of receptor subtype, most likely by inhibition of glutamate release. (nih.gov)
  • SNAP25Δ3 homozygote mice exhibited normal presynaptic inhibition by GABA B receptors, which inhibit VGCCs, but defective presynaptic inhibition by receptors that work directly on the SNARE complex, such as 5-hydroxytryptamine (serotonin) 5-HT 1b receptors and adrenergic α 2a receptors. (sciencemag.org)
  • Citalopram enhances serotonin activity as a result of selective reuptake inhibition at the presynaptic neuronal membrane. (medscape.com)
  • We show for the first time that the serotoninergic and glutamatergic receptors are important targets for the effect of FfB on the conditioned fear and spontaneous recovery, in which the ERK signaling pathway appears to be modulated. (frontiersin.org)
  • Direct measurements of the effects of halothane on isolated glutamate receptor-mediated (glutamatergic) excitatory postsynaptic currents (EPSCs), however, have not been reported to date. (nih.gov)
  • Dysregulation of the glutamatergic system and its receptors in medial prefrontal cortex (mPFC) has been implicated in major depressive disorder. (nature.com)
  • Gaiarsa, J.L., Corradetti, R., Cherubini, E. and Ben-Ari, Y. (1990) The allosteric glycine site of the N-methyl-D-aspartate modulates GABAergic-mediated synaptic events in neonatal rat CA3 hippocampal neurons. (springer.com)
  • Indeed, most neurotransmitter receptors expressed on neurons are also expressed by astrocytes ( 5 ). (pnas.org)
  • Several molecular and biophysical mechanisms contribute to the phenomenon of sensitization and persistent pain, including upregulation of sensory neuron- specific sodium channels and vanilloid receptors, phenotypic switching of large myelinated axons, sprouting within the dorsal horn, and loss of inhibitory neurons due to apoptotic cell death. (spidertech.com)
  • We set up a novel functional neuroimaging approach to map global effects of locally induced activation of specific midbrain projection neurons using chemogenetics (Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-technology) combined with pharmacological magnetic resonance imaging (phMRI) in the rat mesocorticolimbic system. (readbyqxmd.com)
  • Prostanoid receptors: subtypes and signaling. (semanticscholar.org)
  • Of the five dopamine receptor subtypes, the D2 receptor subtype (DRD2) has been extensively studied in alcoholism [ 13 - 23 ]. (mdpi.com)
  • Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. (springer.com)
  • Slices of hippocampal area CA1 were employed to test the hypothesis that the release of glutamate and aspartate is regulated by the activation of excitatory amino acid autoreceptors. (nih.gov)
  • We tested the hypothesis that astrocyte-derived glutamate activates kainate receptors on hippocampal interneurons. (pnas.org)
  • Benveniste H, Jorgensen MB, Diemer NH, Hansen AJ (1988): Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia. (springer.com)
  • Hippocampal glucocorticoid receptor expression levels in the offspring were detected on postnatal 60 (P60).Cognition function was also detected. (bvsalud.org)
  • Together these results show that cannabinoids have significant neuroprotective effects in this model of ALS and suggest that these beneficial effects may be mediated by non-CB1 receptor mechanisms. (420magazine.com)
  • In vitro studies show it to be a high-affinity antagonist that is neuroprotective in cultures of brain cells exposed to toxic concentrations of the excitatory amino acid glutamate. (ahajournals.org)
  • Exogenous kainate receptor agonists have been shown to modulate inhibitory synaptic transmission in the hippocampus, but the pathways involved in physiological activation of the receptors remain largely unknown. (pnas.org)
  • It has been shown in recent years that exogenous kainate receptor agonists modulate inhibitory synaptic transmission in the hippocampus ( 23 - 27 ). (pnas.org)
  • [3] These signals, in the form of neurotransmitter molecules, are received by neurotransmitter receptors present on the surface of the postsynaptic cell. (wikidoc.org)
  • The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. (ox.ac.uk)
  • In a virtual screening for antagonists that exploit differences in the orthosteric binding site of GluN1 and GluN3 subunits, we identified a novel glycine site antagonist, 1-thioxo-1,2-dihydro-[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one (TK40). (eurekamag.com)
  • may also block L-type calcium channels independently of its effects on opioid receptors. (sigmaaldrich.com)
  • Recent findings Nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors consistently reduce postoperative opioid consumption. (ovid.com)
  • Sig1R was originally thought to be an opioid receptor. (bvsalud.org)
  • Effects of halothane on glutamate receptor-mediated excitatory postsynaptic currents. (nih.gov)
  • Thus, the activation of excitatory amino acid receptors has both presynaptic and postsynaptic effects. (nih.gov)
  • LTP improves the postsynaptic cell's sensitivity to neurotransmitter in large part by increasing the activity of existing receptors and by increasing the number of receptors on the postsynaptic cell surface. (wikidoc.org)
  • Thus, CB1 receptor activation can potentially limit the release and postsynaptic effects of excitotoxic glutamate (5⇓6⇓7⇓8⇓, 20)⇓, thereby providing endogenous protection against excitotoxicity. (420magazine.com)
  • There are five major classes of antidepressants used in clinic: monoamine oxidase inhibitors, tricyclic antidepressants, serotonin reuptake inhibitors, dopamine reuptake inhibitors, and selective norepinephrine reuptake inhibitors [ 9 ]. (alliedacademies.org)
  • Currently available treatment options for people suffering from MDD depend on the use of antidepressant medications, which are mostly monoaminergic agents, such as selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), selective norepinephrine or dual serotonin-norepinephrine reuptake inhibitors (SNRIs) and monoamine oxidase inhibitors (MAOIs) [ 8 ]. (clinmedjournals.org)
  • These residues are located at the edge of the binding pocket, suggesting that large antagonists may be necessary for subtype specificity. (aspetjournals.org)
  • Antagonists of metabotropic glutamate receptor subtype 5 (mGluR5), which modulate excitatory neurotransmission, are in clinical trials for fragile X syndrome, a major genetic cause of intellectual disabilities. (sciencemag.org)
  • Discovery of elevated metabotropic glutamate receptor subtype 5 (mGluR5)-mediated signaling and protein synthesis in fragile X knockout mice ( 53 - 56 ) provided the rationale for testing mGluR5 antagonists in ongoing fragile X clinical trials. (sciencemag.org)
  • Gill et al (2002) Pharmacological characterization of Ro 63-1908 (1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N -methyl-D-aspartate antagonist. (tocris.com)
  • The assay selectively identifies allosteric modulators by using supramaximal concentrations of glutamate and glycine to minimize detection of competitive antagonists. (nih.gov)
  • We used BTBR T+tf/J (BTBR) mice, an established model with robust behavioral phenotypes relevant to the three diagnostic behavioral symptoms of autism-unusual social interactions, impaired communication, and repetitive behaviors-to probe the efficacy of a selective negative allosteric modulator of the mGluR5 receptor, GRN-529. (sciencemag.org)
  • Simultaneously stimulating receptors that act through both mechanisms showed synergistic inhibitory effects. (sciencemag.org)
  • However, it is not well understood how glutamate, the excitatory transmitter, activates the receptors on inhibitory interneurons. (pnas.org)
  • Activation of CB1 receptors in the CNS by elevated levels of cannabinoids has an inhibitory effect on neurotransmitter release and cellular calcium influx. (420magazine.com)
  • The recent discovery of endocannabinoids, endogenous metabolites that activate cannabinoid receptors, and an increasing understanding of their synthesis, reuptake, and degradation have focused research into the therapeutic potential of agents that manipulate the endocannabinoid system. (420magazine.com)
  • Our data suggest that an astrocyte-derived, nonsynaptic source of glutamate represents a signaling pathway that can activate neuronal kainate receptors. (pnas.org)
  • 7-Nitroindazole (7-NI) (15, 30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined. (biopsychiatry.com)
  • Neuronal nicotinic ACh receptor antibody in subacute autonomic neuropathy and cancer-related syndromes. (docme.ru)
  • Sigma-1 receptor (S1R) is associated with increased BDNF in hippocampus and with BDNF secretion by brain-derived astrocytes and neuronal cell lines. (bvsalud.org)
  • Effects of polyamines on the binding of [3H]MK-801 to the N-methyl-D-aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site. (semanticscholar.org)
  • This pharmacological profile indicates that kainate receptors were activated during Ca 2+ elevation in astrocytes. (pnas.org)
  • prevents remifentanil-induced hyperalgesia via regulating the expression and function of spinal N-methyl-D-aspartate receptors in vivo and vitro. (jove.com)
  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motoneurons in the spinal cord, brain stem, and motor cortex. (420magazine.com)
  • Conversely, 6-cyano-7-nitro-quinoxaline-2,3-dione, an antagonist active at both quisqualate and kainate receptors, selectively enhanced aspartate release. (nih.gov)
  • Here, we test the hypothesis that calcium-dependent glutamate release from astrocytes ( 10 , 11 , 18 - 20 ) activates kainate receptors on interneurons. (pnas.org)
  • Bonhaus DW, Perry WB, McNamara JO (1990) Decreased density, but not number, of N-methyl- d -aspartate, glycine and phencyclidine binding sites in hippocampus of senescent rats. (springer.com)
  • Frank LM, Brown EN, Wilson M. Trajectory encoding in the hippocampus and entorhinal cortex. (pubmedcentralcanada.ca)
  • Benveniste H, Drejer J, Schousboe A, Diemer NH (1984): Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischaemia monitored by intracerebral microdialysis. (springer.com)
  • Approximately one-third of patients with major depressive disorder do not achieve adequate symptom control despite a series of multiple treatment trials with currently available antidepressant medication (for example a serotonin-selective reuptake inhibitor). (clinicaltrials.gov)
  • BEERSE, Belgium--( BUSINESS WIRE )--The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the European Commission (EC) has approved SPRAVATO ® ▼ (esketamine) nasal spray, in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI), for adults living with treatment-resistant major depressive disorder (TRD). (businesswire.com)
  • In 2008 a proof of concept study was conducted by Pfizer using the NR2B antagonist traxoprodil, which proved that drugs similar to ketamine could be used to treat depressive symptoms without causing the dissociative effect seen in that drug. (wikipedia.org)
  • Albers GW (1990): Potential therapeutic uses of N-methyl-D-aspartate antagonists in cerebral ischemia. (springer.com)
  • G protein-coupled receptors (GPCRs) that couple to G i/o proteins modulate neurotransmission presynaptically by inhibiting exocytosis. (sciencemag.org)
  • These results support the hypothesis that the behavioral effects of PCP-like drugs result at least in part from reduced neurotransmission at excitatory amino acid synapses utilizing N-methyl-D-aspartate preferring receptors. (eurekamag.com)
  • Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists. (nih.gov)
  • Unraveling the mysteries of chronic pain may lead to better treatment options, such as drugs that act specifically on sensory neuron-specific sodium channels or as NR2B-subunit-selective N-methyl-D- aspartate receptor antagonists. (spidertech.com)
  • Here, we show by Schild analysis that TK40 is a potent competitive antagonist with Kb values of 21-63 nM at the GluN1 glycine-binding site of the four recombinant GluN1/N2A-D receptors. (eurekamag.com)
  • Using X-ray crystallography, we show that EVT-101, a GluN2B antagonist structurally unrelated to the classic phenylethanolamine pharmacophore, binds at the same GluN1/GluN2B dimer interface as ifenprodil but adopts a remarkably different binding mode involving a distinct subcavity and receptor interactions. (aspetjournals.org)
  • Acetylcholine released after vagal stimulation binds muscarinic receptors on the surface of sinoatrial and atrioventricular nodal cells and atrial myocytes, triggering a G-protein-signaling cascade that stimulates I KACh and modulates the activity of several other ion channels and enzymes. (jneurosci.org)
  • 4-Hydroxytamoxifen (4-HT) is the active metabolite of tamoxifen which binds estrogen receptors (ER) and estrogen-related receptors (ERR) with estrogenic and anti-estrogenic effects. (sigmaaldrich.com)
  • p110delta(-/-) B cells proliferate poorly in response to B cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B, and are prone to apoptosis. (jove.com)
  • When already activated by calcium, AC1 can be synergistically activated by stimulatory G protein-coupled receptors like β-adrenergic receptor. (physiology.org)
  • The alpha-2-delta receptor modulators such as gabapentin have shown early promising results in multimodal analgesia. (ovid.com)
  • Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excito toxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. (420magazine.com)
  • 9-THC mediates the majority of its activities through stimulation of cannabinoid receptors (CB), notably CB1, which are expressed throughout the CNS (Matsuda et al. (420magazine.com)
  • In fibroblast cells transfected with α1a receptors, A-61603 more potently stimulated phosphoinositide hydrolysis than norepinephrine, and was antagonized by prazosin. (sigmaaldrich.com)
  • Grieder et al (2012) Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal. (tocris.com)
  • In this review, we discuss some of the evidence suggesting that alternative splicing of candidate genes such as DRD2 (encoding dopamine D2 receptor) may form the basis of the mechanisms underlying the pathophysiology of alcoholism. (mdpi.com)
  • Bäckström and Hyytiä (2006) Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking. (tocris.com)
  • We firstly investigated the effects of TDZD-8, a selective GSK-3? (jove.com)
  • A selective N-methyl-D-aspartate antagonist, DL-2-amino-5-phosphonovalerate, was found to produce PCP-like catalepsy, discriminative stimulus effects, and stereotyped operant responding in pigeons when administered intramuscularly. (eurekamag.com)
  • AIMS: This study aimed to evaluate the effects of the sigma-1 receptor (S1R) on atrial fibrillation (AF) susceptibility in rats. (bvsalud.org)
  • By comparison, SNX-111, an N-type voltage-sensitive calcium channel antagonist that is also derived from cone snail venom, produced significant motor impairment at a dose (3.0 pmol, i.t.) that was only partially efficacious in the formalin test. (nih.gov)
  • Capsaicin-sensitive afferent fibers arising from the viscera and peripheral tissues express the transient receptor potential vanilloid subfamily member 1 (TRPV1) ( 8 , 9 ). (physiology.org)
  • Because the primary symptoms of autism and fragile X differ in qualitative features, and mouse models of autism and fragile X display sharply divergent phenotypes, testing mGluR5 antagonists in specific assays of mouse behavioral phenotypes that optimize relevance to the diagnostic symptoms of autism would be most informative for translational goals. (sciencemag.org)
  • Interestingly, both ionotropic glutamate receptors and alpha7 nicotinic receptors are mainly present in the brain. (hindawi.com)