Effect of flumazenil in a model of acute alcohol intoxication in rats.
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.
Lheureux
P
P
Emergency Department (Acute Poisoning Unit), Erasme University Hospital, Brussels, Belgium.
Fontaine
J
J
Askenasi
R
R
D000435:Alcoholic Intoxication / Q000523:psychology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology*; D008297:Male; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D005442:Flumazenil