Turek Fred W, Gillette Martha U
Department of Neurobiology and Physiology, Center for Sleep and Circadian Biology, Northwestern University, 2205 Tech Drive, Hogan Hall 2-160, Evanston, IL 60208, USA.
Sleep Med. 2004 Nov;5(6):523-32. doi: 10.1016/j.sleep.2004.07.009.
Circadian rhythm sleep disorders (CRSDs), whether chronic or transient, affect a broad range of individuals, including many elderly, those with severe visual impairments, shift workers, and jet travelers moving rapidly across many time zones. In addition, various forms of insomnia affect another large sector of the population. A feature common among CRSDs and some forms of insomnia is sensitivity to the hormone melatonin, which is secreted by the pineal gland. Accumulating evidence suggests that melatonin may regulate the circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the light-dark cycle is the primary signal that entrains the circadian clock to environmental cycles, exogenous melatonin has been shown to entrain the clock in individuals with no light perception and free-running circadian rhythms. Furthermore, studies have reported beneficial effects of melatonin for treatment of certain insomnias. Together, these studies suggest that melatonin may be useful for treating some insomnias and CRSDs. In these contexts, use of melatonin as a supplement has been popular in the United States. Unfortunately, the therapeutic potential of melatonin has been difficult to realize in clinical trials, possibly owing to non-specific actions of the agent and its unfavorable pharmacokinetic properties when administered orally. In an attempt to take advantage of the therapeutic opportunities available through the brain's melatonin system, researchers have developed several melatonin agonists with improved properties in comparison to melatonin. Some of these agents are now in clinical trials for treatment of insomnia or CRSDs.
昼夜节律性睡眠障碍（CRSDs），无论是慢性的还是短暂的，都影响着广泛的人群，包括许多老年人、严重视力障碍者、轮班工作者以及快速跨越多个时区的乘飞机旅行者。此外，各种形式的失眠影响着另一大群体。CRSDs和某些形式的失眠的一个共同特征是对松果体分泌的褪黑素敏感。越来越多的证据表明，褪黑素可能调节位于下丘脑视交叉上核（SCN）的生物钟。虽然明暗周期是使生物钟与环境周期同步的主要信号，但外源性褪黑素已被证明能使没有光感知和自由运行的昼夜节律的个体的生物钟同步。此外，研究报告了褪黑素对治疗某些失眠症的有益作用。这些研究共同表明，褪黑素可能对治疗某些失眠症和CRSDs有用。在这些情况下，褪黑素作为补充剂在美国很受欢迎。不幸的是，褪黑素的治疗潜力在临床试验中一直难以实现，这可能是由于该药物的非特异性作用及其口服时不利的药代动力学特性。为了利用通过大脑褪黑素系统获得的治疗机会，研究人员已经开发出了几种与褪黑素相比具有更好特性的褪黑素激动剂。其中一些药物目前正在进行治疗失眠或CRSDs的临床试验。
