MELATONIN AND SLEEP IN HUMANS

Early studies on the physiological effects of melatonin typically repo rted hypnotic 'side-effects'. Later studies, specifically addressing t his action, failed to reliably replicate hypnotic effects using standa rd polysomnography. This difference may be related to differences in t he basic physiological action of melatonin compared with more conventi onal hypnotics. It is suggested that melatonin exerts a hypnotic effec t through thermoregulatory mechanisms. By lowering core body temperatu re, melatonin reduces arousal and increases sleep-propensity. Thus, in humans, one role of melatonin is to transduce the light-dark cycle an d define a window-of-opportunity in which sleep-propensity is enhanced . As such, melatonin is likely to be an effective hypnotic agent for s leep disruption associated with elevated temperature due to low circul ating melatonin levels. The combined circadian and hypnotic effects of melatonin suggest a synergistic action in the treatment of sleep diso rders related to the inappropriate timing of sleep and wakefulness. Ad juvant melatonin may also improve sleep disruption caused by drugs kno wn to alter normal melatonin production (e.g., beta-blockers and benzo diazepines). If melatonin is to be developed as a successful clinical treatment, differences between the pharmacological profile following e xogenous administration and the normal endogenous rhythm should be min imized. Continued development as a useful clinical tool requires contr ol of both the amplitude and duration of the exogenous melatonin pulse . There is a need to develop novel drug delivery systems that can reli ably produce a square-wave pulse of melatonin at physiological levels for 8-10 hr duration.