Differential Effects of Flunitrazepam on Human Sleep in Combination with Flumazenil

The experiments reported here were designed to characterize in detail the spectrum of activity of flunitrazepam in human sleep. The direct and residual effects of flunitrazepam, as well as the antagonism by flumazenil, an antagonist of benzodiazepine receptors, were studied in 28 normal subjects recorded in the sleep laboratory. The five categories of variables--sleep-wake balance, sleep organization, orthodox sleep, phasic events in sleep, and sleep waveforms--were all modified by flunitrazepam. Some of these modifications were observed only on the drug night and were antagonized by flumazenil, whereas others persisted in the placebo postdrug night and were not antagonized by flumazenil. A few variables showed changes intermediate between these two types of reactivity. The results do not fit well with the multiple benzodiazepine receptors theory, but instead support the concept of spare receptors. Along these lines, the study of the reactivity of sleep components to ligands of benzodiazepine receptors can contribute to the better understanding of the neuronal systems involved in their control.