The effects of daytime melatonin treatment (0·3 mg) on cAMP and cGMP levels in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were investigated in 14 normal human subjects (age ... 26·2 3·2 years). Plasma levels of cAMP, cGMP and melatonin were measured before and at intervals for 3 h after the treatment was administered at 1300 h. Plasma melatonin concentrations reached peak levels 1 h after the treatment (mean .. 182·3 43·5 pg/ml). The mean areas under the curve (AUC) for the

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... ime-cGMP concentration curves in PPP and in PRP were significantly increased after melatonin treatment compared with those observed after placebo treatment (P=0·001). No significant difference in cGMP levels was observed between PPP and PRP. Increase in self-reported sleepiness after melatonin treatment positively correlated with increase in plasma cGMP levels (r=0·92). The mean AUC for the time-cAMP concentration in PRP, but not in PPP, was increased 1 h after melatonin treatment compared with that observed after placebo treatment, but not thereafter. No correlation between individual PRP or PPP cAMP levels and subjective sleepiness was observed. These results demonstrate a stimulating effect of melatonin treatment on plasma cGMP levels in humans and suggest a correlation between the increase in circulating cGMP levels and the sleep-promoting effect of the pineal hormone.