Melatonin and sleep in humans

Abstract

Early studies on the physiological effects of melatonin typically reported hypnotic 'side-effects' . Later studies, specifically addressing this action, failed to reliably replicate hypnotic effects using standard polysomnography . This difference may be related to differences in the basic physiological action of melatonin compared with more conventional hypnotics. It is suggested that melatonin exerts a hypnotic effect through thermoregulatory mechanisms. By lowering core body temperature, melatonin reduces arousal and increases sleep-propensity. Thus, in humans, one role of melatonin is to transduce the light-dark cycle and define a window-of-opportunity in which sleep-propensity is enhanced. As such, melatonin is likely to be an effective hypnotic agent for sleep disruption associated with elevated temperature due to low circulating melatonin levels. The combined circadian and hypnotic effects of melatonin suggest a synergistic action in the treatment of sleep disorders related to the inappropriate timing of sleep and wakefulness. Adjuvant melatonin may also improve sleep disruption caused by drugs known to alter normal melatonin production ( e g , P-blockers and benzodiazepines). If melatonin is to be developed as a successful clinical treatment, differences between the pharmacological profile following exogenous administration and the normal endogenous rhythm should be minimized. Continued development as a useful clinical tool requires control of both the amplitude and duration of the exogenous melatonin pulse. There is a need to develop novel drug delivery systems that can reliably produce a square-wave pulse of melatonin at physiological levels for 8-10 hr duration.

Changes in sleepiness and body temperature precede nocturnal sleep onset: Evidence from a polysomnographic study in young men

“…A significant body of research supports the and reinforced with thin, porous surgical tape. In addition, hypothesis that the pineal hormone melatonin may mediate tympanic (Sheridan Catheter Corp., Argyle, NY, USA) and changes in sleep propensity via thermoregulatory effects rectal thermistors (YSI-4491E, Yellow Springs Instuments, (Dawson and Encel 1993;Brown 1994;Dollins et al 1994; OH, USA) were inserted. Thermistors were connected to a Cagnacci 1996; Reid et al 1996;Heuvel et al 1997;Hughes Minilogger ambulatory recording system (Minimitter, Sun and Badia 1997).…”

New Prognostic Biomarkers of Mitochondrial Oxidative Stress in Septic Patients

“…Melatonin has a very short half-life and is predominantly metabolized to 6-sulfatoxymelatonin in the liver and is excreted in urine. Melatonin is involved in the regulation of sleep; moreover, it has anti-inflammatory, antioxidant, and antiapoptotic effects and preserves mitochondrial function (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43).…”

“…In this regard, melatonin has different potential benefit effects (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). Melatonin exhibits anti-inflammatory effects because it decreases the liberation of proinflammatory cytokines (e.g.…”

Aging and oxygen toxicity: Relation to changes in melatonin

“…Melatonin's potentially beneficial effects against the degenerative signs of aging relate not only to its free radical and antioxidant activities (9,36,47), but also to its ability to synchronize circadian rhythms (122) promote sleep (123), stimulate immune function (102), and to its general protective effect in cells (124) (Fig. 4).…”