Biomaterial Database

Ethanol and the GABA receptor complex: studies with the partial inverse benzodiazepine receptor agonist Ro 15-4513. 1988

J R Glowa, and J Crawley, and P D Suzdak, and S M Paul

Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.

Ethanol potentiates GABA-receptor-mediated Cl- ion flux in vitro and, at similar concentrations, has anxiolytic and intoxicating properties in vivo. The imidazobenzodiazepine, Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-meth-6-oxo-4H- imidazo(1,5-a)(1,4)benzodiazepine-3-carboxylate), is a potent partial inverse agonist of the benzodiazepine/GABA receptor which can antagonize the in vitro actions of ethanol in potentiating GABA receptor-mediated Cl- ion flux. Moreover, several of the behavioral effects of ethanol are also antagonized by Ro 15-4513, and these effects can be demonstrated in several paradigms at doses of Ro 15-4513 that do not produce opposite behavioral effects. In contrast, in our studies, other benzodiazepine receptor antagonist and inverse agonists, including Ro 15-1788, FG-7142, and beta-CCE were not able to antagonize these biochemical or behavioral effects of ethanol at doses that were without intrinsic effects. However, both Ro 15-1788 and beta-CCE blocked the antagonism of ethanol's effects by Ro 15-4513, suggesting a role for the GABA receptor complex in the actions of ethanol. These studies provide further evidence that GABAergic neurones may mediate at least some of the behavioral and biochemical actions of low-to-moderate doses of ethanol.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010424	Pentobarbital	A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236)	Mebubarbital,Mebumal,Diabutal,Etaminal,Ethaminal,Nembutal,Pentobarbital Sodium,Pentobarbital, Monosodium Salt,Pentobarbitone,Sagatal,Monosodium Salt Pentobarbital
D011963	Receptors, GABA-A	Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.	Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D002713	Chlorine	An element with atomic symbol Cl, atomic number 17, and atomic weight 35, and member of the halogen family.	Chlorine Gas,Chlorine-35,Cl2 Gas,Chlorine 35,Gas, Chlorine,Gas, Cl2
D003220	Conflict, Psychological	The internal individual struggle resulting from incompatible or opposing needs, drives, or external and internal demands. In group interactions, competitive or opposing action of incompatibles: antagonistic state or action (as of divergent ideas, interests, or persons). (from Merriam-Webster's Collegiate Dictionary, 10th ed)	Conflict, Psychology,Psychological Conflict,Psychological Conflicts
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
D000431	Ethanol	A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.	Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000435	Alcoholic Intoxication	An acute brain syndrome which results from the excessive ingestion of ETHANOL or ALCOHOLIC BEVERAGES.	Drunkenness,Intoxication, Alcoholic,Drunkennesses
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
D001386	Azides	Organic or inorganic compounds that contain the -N3 group.	Azide