Publication Date:
1986-12-05
Description:
Ethanol, at pharmacologically relevant concentrations of 20 to 100 mM, stimulates gamma-aminobutyric (GABA) receptor-mediated uptake of 36Cl-labeled chlorine into isolated brain vesicles. One drug that acts at GABA-benzodiazepine receptors, the imidazobenzodiazepine Ro15-4513, has been found to be a potent antagonist of ethanol-stimulated 36Cl- uptake into brain vesicles, but it fails to antagonize either pentobarbital- or muscimol-stimulated 36Cl- uptake. Pretreatment of rats with Ro15-4513 blocks the anticonflict activity of low doses of ethanol (but not pentobarbital) as well as the behavioral intoxication observed with higher doses of ethanol. The effects of Ro15-4513 in antagonizing ethanol-stimulated 36Cl- uptake and behavior are completely blocked by benzodiazepine receptor antagonists. However, other benzodiazepine receptor inverse agonists fail to antagonize the actions of ethanol in vitro or in vivo, suggesting a novel interaction of Ro15-4513 with the GABA receptor-coupled chloride ion channel complex. The identification of a selective benzodiazepine antagonist of ethanol-stimulated 36Cl- uptake in vitro that blocks the anxiolytic and intoxicating actions of ethanol suggests that many of the neuropharmacologic actions of ethanol may be mediated via central GABA receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzdak, P D -- Glowa, J R -- Crawley, J N -- Schwartz, R D -- Skolnick, P -- Paul, S M -- New York, N.Y. -- Science. 1986 Dec 5;234(4781):1243-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3022383" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Anxiety/drug effects
;
Azides/*pharmacology
;
Benzodiazepines/*pharmacology
;
Chlorides/metabolism
;
Ethanol/*antagonists & inhibitors
;
Flumazenil/pharmacology
;
Male
;
Pyrazoles/pharmacology
;
Rats
;
Rats, Inbred Strains
;
Receptors, GABA-A/drug effects
;
Synaptosomes/drug effects
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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