Flumazenil. A preliminary review of its benzodiazepine antagonist properties, intrinsic activity and therapeutic use

Abstract

Flumazenil, a 1,4-imidazobenzodiazepine, is a specific benzodiazepine antagonist which is indicated for use when the effect of a benzodiazepine must be quickly attenuated or terminated. Following intravenous administration, the onset of clinically apparent benzodiazepine antagonism usually occurs within 1 to 5 minutes. Although flumazenil has a short elimination half-life of about 1 hour, a single intravenous dose of up to 1 mg is usually sufficient to attain and maintain for about 2 hours the desired level of consciousness after general anaesthesia or conscious to moderate sedation induced by benzodiazepines. After intoxication with high doses of benzodiazepines the initial single dose of flumazenil will require supplementing with repeated low intravenous doses or an infusion (0.1 mg/h) to maintain a state of wakefulness. Flumazenil is well tolerated, and since it reliably attenuates or reverses the central effects of benzodiazepines and is specific for these drugs, it facilitates diagnosis by eliminating benzodiazepine intoxication in patients in whom the cause of unconsciousness is unknown. While results of some studies suggested that flumazanil may have intrinsic benzodiazepine partial agonist or inverse agonist activity, this is unlikely to be clinically important with usual doses. Thus, flumazenil is a very promising, effective, short acting benzodiazepine antagonist which is well tolerated by most patients. Undoubtedly, its full clinical potential has yet to be realised.