ACUTE, SUBCHRONIC AND DISCONTINUATION EFFECTS OF ZOPICLONE ON SLEEP EEG AND NOCTURNAL MELATONIN SECRETION

Zopiclone is a new short half-life cyclopyrrolone hypnotic agent actin g at the GABA-benzodiazepine receptor complex. In order to characteriz e its pharmacological profile, the effects of 7.5 mg zopiclone on noct urnal melatonin secretion were investigated under polysomnographic con trol in 11 healthy subjects following acute and subchronic administrat ion as well as after abrupt discontinuation of the drug. No effect of zopiclone on the melatonin plasma levels could be observed. Regarding both total melatonin production and the temporal pattern of melatonin secretion during the night, there was no difference between placebo ba seline condition, acute and subchronic administration, and discontinua tion. In contrast, the sleep EEG data demonstrated the hypnotic effica cy of zopiclone under acute administration and indicated a rebound ins omnia after abrupt discontinuation. Moreover, alterations of sleep arc hitecture were found under treatment as well as after discontinuation. Whereas, with regard to sleep EEG parameters, zopiclone appears to be comparable with some short-acting benzodiazepines, a discrepancy betw een the missing effect of zopiclone on pineal function and the suppres sing influence of benzodiazepines known from the literature becomes ob vious. The fact that zopiclone does not interfere with nocturnal melat onin secretion at pharmacologically active doses as indicated by alter ations in sleep EEG parameters might possibly point to a pharmacodynam ic difference between the two drug classes.