CLINICAL STUDIES OF INDUCTION AGENTS XLIII: FLUNITRAZEPAM

Flunitrazepam (Ro 5-4200) has been studied as an induction agent in 220 volunteers or patients. It was assumed to be 10 times as potent as diazepam. The maximum soporific effect did not occur until 90-120 s after injection. There was great individual variation in response to flunitrazepam and some patients did not lose consciousness even after receiving 6 mg (approximately 0.1 mg/kg). Opiate premedication enhanced its action, but delayed recovery. There was a dose-related increase in minor respiratory upset with flunitrazepam in unpremedicated patients and a high frequency of arterial hypotension following large doses given to patients who had received opiate premedication. Venous sequelae were no more frequent than after comparable doses of diazepam. Flunitrazepam was not a very satisfactory drug for the induction of anaesthesia, and recovery was too prolonged for routine use. Flunitrazepam (Ro 5-4200) is a relatively new benzo-diazepine, related to diazepam (fig. 1) and considered to be about 10 times as potent as the established com-pound. As in the case of diazepam, it is insoluble in water and is available for i.m. or i.v. injection in a DIAZEPAM FLUNITRAZEPAM FIG. 1. Structural formulae of diazepam and flunitrazepam. clear organic solution, made up to 1 mg/ml with a supplied diluent. It has been widely used in anaes-thetic practice, particularly in continental Europe and South America, both as pre-anaesthetic medication, for induction of anaesthesia and as a mild sedative. These early studies show that flunitrazepam has an effect similar to that of an equivalent dose of diazepam