Biomaterial Database

Interaction of benzodiazepines with central nervous glycine receptors: possible mechanism of action. 1974

A B Young, and S R Zukin, and S H Snyder

Interaction of 21 benzodiazepines with the glycine receptor in the brainstem and spinal cord of rat have been evaluated in terms of their displacement of [(3)H]strychinine binding. The rank order of potency of the 21 drugs in displacing specific [(3)H]strychinine binding correlates (p < 0.005) with their rank order of potency in a vareity of pharmacological and behavioral tests in humans and animals that predict clinical efficacy. There is a 50-fold variation in potency of the series of benzodiazepines with mean effective dose (ED(50)) values ranging from 19muM to > 1000 muM. Diazepam (Valium(R)) and chlordiazepoxide (Librium(R)) have ED(50)'s of 26 muM and 200 muM, respectively, whereas the ED(50) for glycine is 25 muM. The inhibitory effects of 10 of the agents in two other central nervous system membrane receptor assays, for the opiate receptor and the muscarinic cholinergic receptor, do not correlate with any of the in vivo pharmacologic and behavioral tests. The benzodiazepines may exert their antianxiety, anticonvulsant and muscle-relaxant effects by mimicking the effects of the neurotransmitter glycine at its central nervous system receptor sites.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009125	Muscle Relaxants, Central	A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358)	Centrally Acting Muscle Relaxants,Central Muscle Relaxants,Relaxants, Central Muscle
D010640	Phenothiazines	Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.
D011950	Receptors, Cholinergic	Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.	ACh Receptor,Acetylcholine Receptor,Acetylcholine Receptors,Cholinergic Receptor,Cholinergic Receptors,Cholinoceptive Sites,Cholinoceptor,Cholinoceptors,Receptors, Acetylcholine,ACh Receptors,Receptors, ACh,Receptor, ACh,Receptor, Acetylcholine,Receptor, Cholinergic,Sites, Cholinoceptive
D011955	Receptors, Drug	Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.	Drug Receptors,Drug Receptor,Receptor, Drug
D001933	Brain Stem	The part of the brain that connects the CEREBRAL HEMISPHERES with the SPINAL CORD. It consists of the MESENCEPHALON; PONS; and MEDULLA OBLONGATA.	Brainstem,Truncus Cerebri,Brain Stems,Brainstems,Cerebri, Truncus,Cerebrus, Truncus,Truncus Cerebrus
D002707	Chlordiazepoxide	An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal.	Methaminodiazepoxide,7-Chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide,7-Chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amine 4-oxide,Chlordiazepoxide Hydrobromide,Chlordiazepoxide Hydrochloride,Chlordiazepoxide Monohydrochloride,Chlordiazepoxide Perchlorate,Chlozepid,Elenium,Librium,7 Chloro 2 methylamino 5 phenyl 3H 1,4 benzodiazepine 4 oxide,7 Chloro N methyl 5 phenyl 3H 1,4 benzodiazepin 2 amine 4 oxide,Hydrobromide, Chlordiazepoxide,Hydrochloride, Chlordiazepoxide,Monohydrochloride, Chlordiazepoxide,Perchlorate, Chlordiazepoxide
D003975	Diazepam	A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.	7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005998	Glycine	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.	Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium