Differential Effects of Flunitrazepam on Human Sleep in Combination with Flumazenil

Abstract

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.

Depressive Effects on the Central Nervous System and Underlying Mechanism of the Enzymatic Extract and Its Phlorotannin-Rich Fraction fromEcklonia cavaEdible Brown Seaweed

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Effects of Some H1-Antagonists on the Sleep-Wake Cycle in Sleep-Disturbed Rats

“…From these findings, it became clear that benzodiazepines produced an increase in the quantity of sleep, but the sleep quality deteriorated. Although the mechanism of the sleep quality deterioration induced by benzodiazepine is not clear, it is almost certain that the decrease in delta activity by benzodiazepines may not be mediated by benzodiazepine receptors (17,23).…”

The GABA A receptor antagonist picrotoxin attenuates most sleep changes induced by progesterone

“…Interestingly, the present effects of picrotoxin on sleep are very similar to those reported for flumazenil, an antagonist of the benzodiazepine binding site on the GABA A receptor complex, in humans. A single oral bedtime dose of 100 mg flumazenil has been shown to prolong sleep onset latency and to shorten the non-REM-REM cycles, while having little effect on the EEG waves during non-REMS (Gaillard and Blois 1989).…”