Article date: November 1986
By: U Klotz, G Ziegler, B Rosenkranz, G Mikus, in Volume 22, Issue 5, pages 513-520
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.
DOI: 10.1111/j.1365-2125.1986.tb02929.x
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