Effect of flumazenil on midazolam-induced amnesia

We have studied the effect of i.v. flumazenil 0.01 mg kg-1 on the amnesia and sedation caused by midazolam 2 mg and 5 mg i.v. in volunteers in order to determine the relationship between the actions of the antagonist on these two effects. Midazolam caused dose-dependent central neural depression as assessed by critical flicker fusion frequency, and dose-dependent amnesia for word cards. In subjects given flumazenil 5 min after administration of midazolam, fusion frequency readings and memory were restored to levels comparable to those before midazolam administration. These two effects of flumazenil were similar in time course and extent, suggesting that they share the same mechanism of action. Flumazenil given alone had no effect on memory. The study has demonstrated anterograde amnesia following benzodiazepine administration and antagonism by flumazenil. There was neither retrograde amnesia nor retrograde antagonism of amnesia.