Clinical Use of Benzodiazepine Antagonists
The benzodiazepins were introducted in the early sixties. Their various pharmacological properties and their high toxic/therapeutic ratio explain the wide development of their clinical use (and abuse?). Their mechanism of action on the central nervous system (CNS) was only elucidated in 1977 when high affinity binding sites, closely related to GABA-ergic synapses, were discovered in the mammalian cerebral cortex and related to the pharmacologic action of benzodiazepines [1, 2]. A specific antagonist of benzodiazepine-receptors (Ro 15-1788 — flumazenil), able to inhibit all the effects of classical benzodiazepines without inducing any own action, was discovered by Hunkeleer et al. in 1981 .
KeywordsHepatic Encephalopathy Inverse Agonist Central Receptor Partial Inverse Agonist Mammalian Cerebral Cortex
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- 5.Polc P, Bonetti EP, Schaffner R, Haefely W (1982) A three-state model of the benzodiazepine receptor explains the interaction between the benzodiazepine antagonist Ro 15-1788, BZD tranquilizers, B-carbolines, and phenobarbitone. Naunyn-Schmiedelberg’s Arch Pharmacol 321:260–264.CrossRefGoogle Scholar
- 6.Richards JG, Mohler H, Haefely W (1982) Benzodiazepine binding sites: receptors or acceptors? TIPS 3:233–235.Google Scholar
- 11.Lheureux P, Askenasi R (1987) Specific treatment of benzodiazepine overdose. Human Toxicology (in press).Google Scholar
- 13.Klotz U, Ziegler G, Reimann IW (1984) Pharmacokinetics of the selective benzodiazepine antagonist RO-15-1788 in man. Eur Clin Pharmacol 27:115–117.Google Scholar
- 15.Lheureux P, Askenasi R (1986) Benzodiazepine antagonist RO 15-1788 in acute alcohol intoxication. Toxicology Letters 31(s): 155 (abstract).Google Scholar
- 25.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 (letter).Google Scholar