The Effects of a Benzodiazepine Antagonist Ro 15–1788 in the Presence of Stable Concentrations of Midazolam

Abstract

The benzodiazepine antagonist Ro 15-1788 [ethyl-8-fluoro-5,6-didydro-5-methyl-6-oxo-4H-imidazo-[1,5-a]-[1,4]-benzo-diazepine-3-carboxylate] was administered in a 10-mg i.v. bolus dose to 7 healthy young adult volunteers to evaluate the drug''s efficacy and duration of action against midazolam. A steady state serum concentration of midazolam was obtained by an initial fast infusion rate of 6.0 mg/min (duration: 10 min) and a maintenance infusion rate of 0.275 mg/min. After administering the antagonist, all subjects opened their eyes without any command in a median time of 36 s (range: 28-48 s). Their personal, temporal and local orientation was reestablished within 54-120 s (median time: 65 s). The subjects fell deeply asleep, again in a median time of 145 min (range: 115-150 min), which was interpreted as an indication of the returning action of midazolam, which was infused for a total period of 210 min. Ro 15-1788 deserves further study as an antagonist, since it could prove useful in the management of benzodiazepine overdosage and in the reversal of benzodiazepine overdosage and in the reversal of benzodiazepine action following surgical anesthesia and in the intensive care.