Time course of antagonism of sedative and amnesic effects of diazepam by flumazenil.

Reversal of the sedative and amnesic effects of intravenous diazepam by the benzodiazepine antagonist flumazenil was investigated in 30 patients undergoing conscious sedation for dental surgery. Verbal memory tasks were administered and patients' subjective ratings of mood were obtained before and after diazepam and then periodically after intravenous administration of flumazenil or placebo under double-blind conditions. Immediate and delayed recall and recognition tests showed that diazepam impaired memory and that flumazenil partially reversed this impairment. The subjective ratings showed that diazepam produced physical and mental sedation and that flumazenil reversed this sedation. The reversal produced a return to presurgery scores for mental sedation but not for physical sedation or memory. For physical sedation, the difference between flumazenil and placebo was not demonstrable for more than 15 min after flumazenil administration; for mental sedation, it was demonstrable for as long as 60 min. The reversal by flumazenil of diazepam-induced memory impairment did not change significantly over time.