Mechanism of action of the benzodiazepines: behavioral aspect. 1980

J Sepinwall, and L Cook

The mechanism of action of benzodiazepines is considered from a behavioral pharmacology perspective, particularly with respect to methods that involve suppression of responding, such as the punishment-conflict model. Four biochemical hypotheses of current interrest are reviewed. 1) Several lines of evidence suggest that the benzodiazepine receptor in brain is related to the antianxiety actions of benzodiazepines, including a high correlation between potency in the binding assay and potency in the test, and some novel nonbenzodiazepine compounds that bind to the receptor and are also active in the conflict tests. 2) The evidence is mixed concerning whether inosine or hypoxanthine may be endogenous ligands for the benzodiazepine receptor. Unlike benzodiazepines, neither inosine nor hypoxanthine antagonizes convulsions induced by pentylenetetraxol in the rat. 3) Much research indicates that gamma-aminobutyric acid (GABA) mediates various electrophysiological and biochemical actions of benzodiazepines. Several studies have also found that picrotoxin or bicuculline block the behavior effects of benzodiazepines, although some conflicting results have been reported. Most available findings suggest that GABA agonists, e.g., muscimol, do not exhibit the antianxiety profile of the benzodiazepines. 4) Additional evidence has accumulated to support the hypothesis that the behavioral actions of the benzodiazepines are mediated by serotonin, possibly with the involvement of GABA.

UI MeSH Term Description Entries
D007042 Hypoxanthines Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.
D007288 Inosine A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)
D008959 Models, Neurological Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D008960 Models, Psychological Theoretical representations that simulate psychological processes and/or social processes. These include the use of mathematical equations, computers, and other electronic equipment. Model, Mental,Model, Psychological,Models, Mental,Models, Psychologic,Psychological Models,Mental Model,Mental Models,Model, Psychologic,Psychologic Model,Psychologic Models,Psychological Model
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
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
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
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors

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