[Beta activation following the intravenous administration of benzodiazepines and the specific antagonist flumazenil (Ro 15-1788)].

Abstract

In a prospective randomized study involving 32 male subjects aged 18 to 38, the effects of flunitrazepam (0.25 to 2 mg/70 kg), lormetazepam (0.5 to 4 mg/70 kg), midazolam (1.5 to 12 mg/70 kg) and diazepam (4 to 32 mg/70 kg) on the beta-activity (13 to 20/s) were investigated. Each subject received four benzodiazepine injections of increasing dosage. The doses were selected so that the lowest had only a slight effect on the test person's condition, while the highest resulted in deep sedation. The increase in beta-activity started off with a latency of 30 to 60 s; it was proportional to the dosage and reached its maximum between the 2. and 3. minutes. The subsequent decrease in beta-activity could be represented by an exponential function. The effect could be cancelled temporarily by administering repeated doses of the specific antagonist, flumazenil (0.1, 0.3 and 0.9 mg/70 kg). The method is suited for describing pharmacodynamic processes, determining equipotential doses of benzodiazepines and detecting the interaction between benzodiazepines and specific antagonists.