Hypothermic action of exogenously administered melatonin is dose-dependent in humans.
The pineal hormone melatonin (MLT) is closely related to sleep initiation and maintenance in humans, and is now used as a potent therapeutic tool for some circadian rhythm sleep disorders. Acute and transient hypothermia induced by exogenously administered MLT (ex-MLT) may play a critical role in the circadian phase shifting and hypnogenic actions. Six healthy young male volunteers (mean age, 22.5 y; age range, 19-24 y), whose endogenous MLT secretion rhythms were previously assessed, took either 0.5 mg, 3 mg, or 9 mg of ex-MLT or a placebo at 0930 h (the average sleep onset time was 0000 h) on a randomized, single-blind, crossover basis. In comparison with placebo, ex-MLT significantly suppressed core body temperature at the 3-mg and 9-mg doses and slightly suppressed core body temperature at the 0.5-mg dose. There was significant positive correlation between the magnitude of core body temperature suppression and the area under the MLT concentration curve as well as the peak MLT concentration after ex-MLT administration. Our study showed that clinical doses of ex-MLT induce hypothermia in a dose-dependent manner. Results suggest that the therapeutic effect of larger doses of ex-MLT should be tested on patients who benefit little from typically lower clinical doses of ex-MLT.
Satoh
K
K
Department of Neuropsychiatry, Akita University School of Medicine, 1-1-1 Hondo, Akita-city, Akita, 010-8543, Japan.
Mishima
K
K
D000328:Adult; D001831:Body Temperature / Q000187:drug effects*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects
D008550:Melatonin