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Human & Experimental Toxicology
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Effect of Flumazenil in a Model of Acute Alcohol Intoxication in Rats

P. Lheureux

Emergency Department (Acute Poisoning Unit), Erasme University Hospital

J. Fontaine

Department of Pharmacology, Pharmacy Institute Free University of Brussels, Belgium

R. Askenasi

Emergency Department (Acute Poisoning Unit), Erasme University Hospital

The ability of high doses of flumazenil to antagonize ethanol-induced sedation was assessed via ethanol-induced loss of the righting reflex (LRR) in rats. Ethanol (3.5-5 g kg-1 i,p) produces a dose-dependent increase in the proportion of animals presenting a LRR response. Flumazenil (0.1 to 1 mg kg-1 i.p) was ineffective in preventing the suppression of the righting reflex and even aggravated it for ethanol dosages of 3.5 and 4.0 g kg-1. These data support the view that flumazenil has no effective 'anti-ethanol' properties. Conversely, the prolongation of mean sleep time provoked by the antidote could be related to the suppression of a putative endogenous inverse-agonist activity at the benzodiazepine receptor, which could be implicated in the mechanism of the acute tolerance to ethanol.

Human & Experimental Toxicology, Vol. 12, No. 2, 177-180 (1993)
DOI: 10.1177/096032719301200215
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