Effect of zopiclone and midazolam on sleep and EEG spectra in a phase-advanced sleep schedule

Midazolam (15 mg), a benzodiazepine (BDZ) hypnotic, and zopiclone (7.5 mg), a non-BDZ hypnotic, were administered to young, healthy subjects prior to bedtime. They went to bed at 2300 hours after taking placebo (PL-23), and then on three occasions at 1900 hour after taking placebo (PL-19) or one of the hypnotics. Advancing bedtime by 4 hour increased the combined value of waking, stage 1, and movement time. Compared to PL-19, both drugs reduced sleep latency and stage 3, and increased stage 2. Spectral analysis of the EEG in non-rapid-eye-movement sleep revealed a declining trend of power density in the low-frequency range in the course of the night. Activity in the 1 to 10 Hz range was markedly depressed by the two hypnotics, whereas activity in the spindle range (11 to 14 Hz) was augmented. The former changes persisted throughout the 12-hour recording period. The fact that both hypnotics bind to BDZ receptors could be responsible for the similar effects on the EEG spectra.