Electroencephalographic effects of benzodiazepines. II. Pharmacodynamic modeling of the electroencephalographic effects of midazolam and diazepam.

The comparative pharmacodynamics of midazolam and diazepam were examined by use of the electroencephalogram as a measure of drug effect on the central nervous system. Intravenous doses of 7.5, 15, and 25 mg midazolam and 15, 30, and 50 mg diazepam were given on repeated occasions to three volunteers. Arterial plasma concentration and electroencephalogram voltage were related with nonparameteric and parametric pharmacodynamic models. The peak increases in voltage (maximal effect) and the slopes of the plasma concentration versus effect curve were similar for both drugs. The half-time of blood:brain equilibration was significantly longer for midazolam than diazepam (4.8 minutes versus 1.6 minutes). Midazolam was found to have an intrinsic steady-state potency that was approximately five times greater than that of diazepam (152 ng/ml versus 958 ng/ml).