Flumazenil: a novel and potent benzodiazepine competitive receptor blocker

ABSTRACT

One of the most rewarding outcomes in the recent research in the field of benzodiazepines [BNZs] is the discovery of BNZ receptors and their association with GABA receptors, together with the discovery of some synthetic BNZ agonists andas antagonists. To the latter group belongs the 1,4-imidazodiazepine derivative-flumazenil which was introduced in 1981. It is shown to be competitive blocker for both types of BNZ receptors, namely, BNZ type-1 which are involved in the anxiolytic effects and BNZ type-2 which are involved in sedation and sleep. Administration of flumazenil [10 micro g/kgi.v] is shown to rapidly antagonize [within minutes] BNZ-induced anxiolytic, sedative,hypnotic, ataxic, anticonvulsant, amnestic and respiratory depressant effects. The major disadvantage of flumazenil is its rapid hepatic metabolism that curtails its oral use. Beside helping in reversal of BNZ- induced intoxication,the drug has been proven to be of value in the diagnosis of unconsciousness of unknown origin, to test for BNZs- involvement and in the improving of consciousness in some cases of hepatic coma. The introduction of flumazenil is expected to give an extended margin of safety to the use of BNZs, but it is hoped that it would not encourage the overwhelming use of these drugs