Mishima K, Satoh K, Shimizu T, Hishikawa Y
Department of Neuropsychiatry, Akita University School of Medicine, Japan.
Psychopharmacology (Berl). 1997 Sep;133(2):168-71. doi: 10.1007/s002130050387.
Six healthy male volunteers (average age = 22.5 years) received orally melatonin (MLT; 3 mg or 9 mg) or placebo at 0930 hours in a randomized, single-blind, cross-over study. Both doses of exogenously administered melatonin (ex-MLT) induced transient, significant suppression of core body temperature (BT) compared to the placebo condition. There was no significant difference in the degree of BT suppression among the two MLT conditions in spite of significantly higher levels of serum MLT with the close of 9 mg, suggesting that there may be a threshold level of ex-MLT inducing the hypothermic action. Daytime administered ex-MLT also induced a significant sleep-inducing effect only in the 9 mg condition, while 3 mg ex-MLT failed to produce statistical significance. These findings suggest that the sleep-inducing action of ex-MLT occurs only at relatively high doses, and this action is probably not due to its BT lowering action. The present study led us to assume that ex-MLT produce its therapeutic effect for circadian rhythm sleep disorders through induction of circadian phase-shifting preceded by an acute, transient hypothermic action rather than light entrainment after setting sleep time by induction of sleep propensity.
在一项随机、单盲、交叉研究中，6名健康男性志愿者（平均年龄 = 22.5岁）于09:30口服褪黑素（MLT；3毫克或9毫克）或安慰剂。与安慰剂组相比，两种剂量的外源性褪黑素（ex-MLT）均引起核心体温（BT）短暂且显著降低。尽管9毫克组血清MLT水平显著更高，但两种MLT组之间的BT降低程度无显著差异，这表明可能存在一个诱导体温降低作用的外源性褪黑素阈值水平。白天服用的外源性褪黑素仅在9毫克组诱导出显著的促眠作用，而3毫克外源性褪黑素未产生统计学意义。这些发现表明，外源性褪黑素的促眠作用仅在相对高剂量时出现，且该作用可能并非因其降低体温的作用。本研究使我们推测，外源性褪黑素通过在急性、短暂的体温降低作用之前诱导昼夜节律相移，而非通过诱导睡眠倾向设定睡眠时间后进行光同步化，从而对昼夜节律性睡眠障碍产生治疗作用。
