Complex effects of melatonin.

The primary function of melatonin in mammals is to transmit information concerning light-dark cycles for the organization of day length dependent on seasonal functions. There is little evidence for an essential role in circadian organization in mammals, in contrast with lower vertebates. It does, however, appear to reinforce physiological functions associated with darkness. Free-running blind and indeed sighted subjects show a close correlation between maximum sleepiness, minimum temperature and peak melatonin secretion. In humans exogenous melatonin will lower core body temperature and induce transient sleepiness in suitable doses and conditions. Similarly it will shift circadian phase, as assessed by a number of marker rhythms. These phase-shifting properties may not be sufficient to synchronize all circadian rhythms in the absence of other time cues. In most normal sighted subjects and a number of blind subjects the sleep-wake cycle can be 'stabilized' to a 24 h period by daily melatonin administration in free-running conditions. However, anomalous results have also been obtained. Daily administration of melatonin (5 mg) appears to fragment sleep in some subjects treated in dim light conditions. This observation requires further investigation since it may compromise the therapeutic potential of both melatonin and its agonists.