werner@aecom.UUCP (Craig Werner) (12/07/86)
! A Selective Imidazobenzodiazepine Antagonist of Ethanol in the Rat.
! Suzdak PD, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM.
! Science 234:1243 (5 Dec 1986)
Ethanol, at pharmacologically relevant concentrations of 20
to 100 mM, stimulates gamma-aminobutyric (GABA) receptor-mediated
uptake of [36]-Cl-labeled chlorine into isolated brain vesicles. One drug
that acts at GABA-benzodiazepine receptros, the imidazobenzodiazepine
Ro15-4513, has been found to be a potent antagonist of ethanol-stimulated
[36]-Cl uptake into brain vesicles, but it fails to antagonize either
pentobarbitol- or muscimol-stimulated Cl uptake. Pretreatment of rats
with Ro15-4513 blocks the anti-conflict activity of low doses of ethanol,
as wells as the behavioral intoxication of observed with higher doses of
Ethanol. The effects of Ro15-4513 in antagonizing ethanol-
stimulated Cl 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
channel complex. The identification of a selective benzodiazepine
antagonist of ethanol stimulated Cl uptake in vitro that blocks the
anxiolytic and intoxicating actions of ethanol suggests that many of the
neuropharmacological actions of ethanol may be mediated via central GABA
receptors.
--
Craig Werner (MD/PhD '91)
!philabs!aecom!werner
(1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517)
"Why is it that half the calories is twice the price?"