Summary
The effect on cognitive and psychomotor performance of the benzodiazepine (BZD) antagonist, flumazenil, in antagonising the central effect, of ethanol in man has been investigated. Eight healthy adult male volunteers, aged 23 to 32 years, participated in the study. Following a loading infusion, stable blood ethanol levels with a mean value of 1.6 g·l−1 were produced by a maintenance infusion. When stable blood levels of ethanol were reached, 5.0 mg flumazenil/placebo was administered intravenously, and after 15 and 75 min a test battery evaluating psychomotor and cognitive functions was applied.
The test battery was sensitive to the test model, but no significant improvement in the test scores could be demonstrated following the administration of flumazenil.
It is concluded that flumazenil has no influence on psychomotor functions in acute ethanol intoxication.
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References
Barret JE, Brady LS, Witkin JM (1985) Behavioral studies with anxiolytic drugs. I. Interactions of the benzodiazepine antagonist Ro 15-1788 with chlordiazepoxide, pentobarbital and ethanol. J Pharmacol Exp Ther 233: 554–559
Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47: 211–218
Cott J, Carlsson A, Engel J, Lindqvist M (1976) Suppression of ethanol-induced locomotor stimulation by GABA-like drugs. Arch Pharmacol 295: 203–209
Darragh A, Lambe R, Kenny M, Brick I, Taafe W, O'Boyle C (1982) Ro 15-1788 antagonises the central effects of diazepam in man without altering diazepam bioavailability. Br J Clin Pharmacol 14: 677–682
Davis W, Ticku MK (1981) Ethanol enhances [3H]-diazepam binding at the benzodiazepine-gamma-aminobutyric acid receptor-ionophore complex. Mol Pharmacol 20: 287–294
File SE, Pellow S (1986) Intrinsic actions of the benzodiazepine receptor antagonist Ro 15 17-88. Psychopharmacology 88: 1–11
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
Van Gorder PN, Hoffman WE, Baugham V, Albrecht RF, Miletich D, Guzman F, Cook JM (1985) Midazolam-ethanol interactions and reversal with a benzodiazepine antagonist. Anesth Analg 64: 129–135
Greenberg DA, Cooper EC, Gordon A, Diamond I (1984) Ethanol and the Gamma-aminobutyric acid-benzodiazepine receptor complex. J Neurochem 42: 1062–1068
Higgitt A, Lader M, Fonagy P (1986) The effects of benzodiazepine antagonist Ro 15-1788 on psycho-psychological performance and measures in normal subjects. Psychopharmacol 89: 395–403
Hunkeler W, Moehler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290: 514–516
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
Lauven PM, Schwilden H, Stoeckel H, Greenblatt DJ (1985) The effects of a benzodiazepine antagonist Ro 15-1788 in the presence of stable concentrations of midazolam. Anesthesiology 63: 61–64
Liljequist S, Engel J (1979) The effect of chronic ethanol administration on central neurotransmitter mechanisms. Med Biol 57: 199–210
Liljequist S, Engel JA (1984) The effects of GABA and benzodiazepine receptor antagonists on the anti-conflict actions of diazepam or ethanol. Pharmacol Biochem Behav 21: 521–525
Moehler H (1983) Benzodiazepine receptors. In: Mandel P, De Fendis FV (eds) Mode of interaction of agonists and antagonists. Raven Press, New York, CNS-receptors — From molecular pharmacology to behaviour: 247–254
O'Sullivan GF, Wade DN (1987) Flumazenil in the management of acute drug overdosage with benzodiazepines and other agents. Clin Pharmacol Ther 42: 254–259
Radlow R, Hurst PM (1985) Temporal relations between blood alcohol concentration and alcohol effect: an experiment with human subjects. Psychopharmacology 85: 260–266
Reisby N, Theilgaard A (1969) The interaction of alcohol and meprobamate in man. Acta Psychiatr Scand [Suppl] 208: 28–39
Schoepf J, Laurian PK, Gaillard JM (1984) Intrinsic activity of the benzodiazepine antagonist Ro 15-1788 in man: An electro-physiological investigation. Pharmacopsychiatry 17: 79–83
Scollo-Lavizzari G, Matthis H (1985) Benzodiazepine antagonist (Ro 15-1788) in ethanol intoxication: A pilot study. Eur Neurol 24: 352–354
Suzdak PD, Glowa JR, Crawley JN, Schwartz R, Skolnick P, Paul SM (1986) A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science 234: 1243–1247
Ticku MK, Burch T (1980) Alterations in gamma-Aminobutyric acid receptor sensitivity following acute and chronic ethanol treatments. J Neurochem 34: 417–423
Wolff J, Carl P, Clausen TG, Mikkelsen BO (1986) Ro 15-1788 for postoperative recovery. A clinical trial in patients undergoing minor surgical procedures under midazolam anaesthesia. Anaesthesia 41: 1001–1006
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Clausen, T.G., Wolff, J., Carl, P. et al. The effect of the benzodiazepine antagonist, flumazenil, on psychometric performance in acute ethanol intoxication in man. Eur J Clin Pharmacol 38, 233–236 (1990). https://doi.org/10.1007/BF00315022
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DOI: https://doi.org/10.1007/BF00315022