Lack of effect of the benzodiazepine antagonist flumazenil (Ro 15-1788) on the performance of healthy subjects during experimentally induced ethanol intoxication

Abstract

Flumazenil is a specific benzodiazepine antagonist. This study was designed to determine whether it also reverses CNS depression due to acute alcohol intoxication. Intoxication was experimentally induced in 6 healthy volunteers by intravenous infusion of ethanol. Individual constant ethanol plasma concentrations in the range 1.47 +/- 0.04 g.l-1 to 1.71 +/- 0.03 g.l-1 were maintained over 6 h. Two doses of flumazenil (0.1 or 0.2 mg.kg-1) and placebo were administered intravenously in a randomized, double-blind, two-way cross-over fashion. A battery of psychometric tests and subjective ratings of mood and performance were performed at baseline and at regular intervals during the study. Before the administration of flumazenil the characteristic symptoms and signs of ethanol intoxication were present in all subjects. Performance (measured by visual analogue scales), reaction time, digit symbol substitution test, and a tracing test, were markedly impaired by ethanol. After the injection of flumazenil three volunteers reported some subjective improvement in performance. However, in none of the subjects was there a difference between either dose of flumazenil and placebo in terms of an improvement in the objective psychometric variables.

Effects of Fentanyl and Low Doses of Alcohol on Neuropsychological Performance in Healthy Subjects

“…Using low doses of alcohol (up to 0.04% BAC) no effects on psychomotor performance were reported [30,31]. At a BAC of 0.15%, Fluckinger et al [32] measured a marked impairment of psychomotor performance. It is not impossible that the effect of a steady-state BAC is smaller than on the ascending part of the BAC curve.…”

Benzodiazepine Antagonists An Update of Their Role in the Emergency Care of Overdose Patients

“…If a patient fails to respond within 2 to 3 min after the end of injection it can be concluded that additional factors and circumstances other than benzodiazepines may be involved (Fantozzi et al 1988). In cases in which different sedative drugs contribute to the comatose state much higher doses have been reported to be necessary which, in single cases, far exceeded lOmg (Fantozzi et al 1988;Fluckiger et al 1988;Lheureux & Askenasi 1988a;Mapelli et al 1988). In successful cases, reinjections after 45 to 60 min are usually necessary to maintain the achieved state of vigilance.…”

“…Before and after flumazenil administration, the volunteers had to undergo a battery of psychometric tests and subjective ratings of mood and performance. No improvement in the objective psychometric variables was observed (Fluckiger et al 1988). Thus, the effect of flumazenil in acute alcohol overdose remains unclear.…”

Amethystic agents influencing toxicodynamics of ethanol

“…Так, антагонист БД-рецепторов Ro 15-1788 (флумазенил) неоднократно оценивался на предмет отрезвляющей активности. Результаты таких исследований оказались весьма противоречивыми [11][12][13]. Поэтому препарат не рекомендуется использовать при отравлениях этанолом тяжёлой степени.…”