Summary
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amrein R, Cano JP, Hartmann D, Ziegler WH, Dubuis R (1979) Clinical and psychometric effects of flunitrazepam observed during the day in relation to pharmacokinetic data. In: Priest RG, Pletscher A, Ward J (eds) Sleep research. Proceedings of the Northern European Symposium on Sleep Research, MTP Press, Lancaster, UK, pp 83–98
Bansky G, Meier PJ, Ziegler WH, Walser H, Schmid M, Huber M (1985) Reversal of hepatic coma by benzodiazepine antagonist (Ro 15-1788). Lancet 1: 1324–1325
Chan AWK (1984) Effects of combined alcohol and benzodiazepine: A review. Drug Alcohol Depend 13: 315–341
Costa E, Corda MG, Epstein B, Forchetti C, Guidotti A (1983) GABA-benzodiazepine interactions. In: Costa E (ed) The benzodiazepines: From molecular biology to clinical practice. Raven Press, New York
Gaillard JM, Blois R (1983) Effect of the benzodiazepine antagonist Ro 15-1788 on flunitrazepam-induced sleep changes. Br J Clin Pharmacol 15: 529–536
Hartmann D, Flückiger A, Ziegler WH, Timm U, Zell M (1988) Experimental model for the investigation of kinetic and/or dynamic interactions between drugs and ethanol in humans. J Pharm Sci (in press)
Higgit A, Lader M, Fonagy P (1986) The effects of benzodiazepine antagonist Ro 15-1788 on psychophysiological, performance and subjective measures in normal subjects. Psychopharmacology 89: 395–403
Hofer P, Scollo-Lavizzari G (1985) Benzodiazepine antagonist Ro 15-1788 in self-poisoning. Diagnostic and therapeutic use. Arch Intern Med 145: 663–664
Hunkeler W, Möhler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefeli W (1981) Selective antagonists of benzodiazepines. Nature 290: 514–516
Klotz U, Ludwig L, Reimann IW (1984) Pharmacokinetics of the selective benzodiazepine antagonist Ro 15-1788 in man, Eur J Clin Pharmacol 27: 115–117
Klotz U, Ziegler G, Ludwig L, Reimann IW (1985) Pharmacodynamic interaction between midazolam and a specific benzodiazepine antagonist in humans. J Clin Pharmacol 25: 400–406
Klotz U, Ziegler G, Rosenkranz B, Mikus G (1986) Does the benzodiazepine antagonist Ro 15-1788 antagonize the action of ethanol? Br J Clin Pharmacol 22: 513–520
Kulonen E (1983) Ethanol and GABA. Med Biol 61: 147–167
Möhler H, Richards JG (1981) Agonist and antagonist benzodiazepine receptor interaction in vitro. Nature 294: 763–765
Roncari G, Ziegler WH, Güntert TW (1986) Pharmacokinetics of Ro 15-1788 in man following intravenous and oral administration. Br J Clin Pharmacol 22: 421–428
Scollo-Lavizzari G, Matthis H (1985) Benzodiazepine antagonist (Ro 15-1788) in ethanol intoxication: A pilot study. Eur Neurol 24: 352–354
Scollo-Lavizzari G, Steinmann E (1985) Reversal of hepatic coma by benzodiazepine antagonist (Ro 15-1788). Lancet 1: 1324–1325
Tran VT, Snyder SH, Major LF, Hawley RJ (1981) GABA receptors are increased in brains of alcoholics. Ann Neurol 9: 289–292
Wechsler D (1964) Die Messung der Intelligenz Erwachsener. Hans Huber, Bern
Wolff J, Carl P, Clausen TG, Mikkelsen BO (1986) Ro 15-1788 for postoperative recovery. A randomized clinical trial in patients undergoing minor surgical procedures under midazolam anaesthesia. Anaesthesia 41: 1001–1006
Ziegler WH, Schalch E (1983) Antagonism of benzodiazepine-induced sedation in man. Sleep 1982, 6th European Congress on Sleep Research, Zurich 1982, pp 427–429
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Flückiger, A., Hartmann, D., Leishman, B. et al. Lack of effect of the benzodiazepine antagonist flumazenil (Ro 15-1788) on the performance of healthy subjects during experimentally induced ethanol intoxication. Eur J Clin Pharmacol 34, 273–276 (1988). https://doi.org/10.1007/BF00540955
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00540955