Does the benzodiazepine antagonist Ro 15-1788 antagonize the action of ethanol?
Ethanol aggravates benzodiazepine-induced central nervous depression by pharmacokinetic and/or pharmacodynamic interactions and Ro 15-1788 reverses promptly the hypnotic effects of benzodiazepines. We therefore studied the acute effects of Ro 15-1788 on the ethanol-induced sedation in six healthy male subjects. Subsequently to an oral loading dose (0.54 g ethanol kg-1) ethanol was infused for 4 h (0.15 g ethanol kg-1 h-1) and steady state blood levels between 0.9 to 1.2 g l-1 were reached within 2 h. At steady state and during the elimination phase of ethanol an intravenous bolus of 0.5 mg Ro 15-1788 or placebo was administered in a randomized, double-blind crossover fashion. The marked sedative effects of ethanol as assessed by visual analogue scales (2 to 6 fold increase in the sedation index), and choice reaction time (25 to 40% prolongation) were not affected by Ro 15-1788. However, the pharmaco-EEG indicated that Ro 15-1788 seems to reverse transiently the ethanol-induced changes in total alpha, delta, and slow alpha bands. There was no pharmacokinetic interaction between both agents since elimination of Ro 15-1788 (t1/2 = 1.2 +/- 0.7 h) and of ethanol (0.17 +/- 0.02 g l-1 h-1) were in good agreement with control values. Thus, it could be concluded that Ro 15-1788 might affect for a short while the action of ethanol by interfering with the benzodiazepine receptors.
D000328:Adult; D002490:Central Nervous System / Q000187:drug effects; D004311:Double-Blind Method; D004347:Drug Interactions; D004569:Electroencephalography; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D005442:Flumazenil / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D011930:Reaction Time / Q000187:drug effects
D000431:Ethanol; D005442:Flumazenil