Pandi-Perumal Seithikurippu R, Srinivasan Venkataramanujan, Poeggeler Burkhard, Hardeland Rüdiger, Cardinali Daniel P
Comprehensive Center for Sleep Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Nat Clin Pract Neurol. 2007 Apr;3(4):221-8. doi: 10.1038/ncpneuro0467.
Melatonin, a chronobiotic that participates in the control of the circadian system, is known for its sleep-promoting effects, which include shortening of sleep latency and lengthening of sleep duration. As a result of its short half-life, melatonin does not exhibit undesirable side effects, and its broad applicability for a variety of sleep problems has been the focus of numerous scientific studies. Melatonin has not, however, received regulatory approval from the US FDA as a drug, because it can be sold freely as a food supplement. Consequently, there has been an active search for patentable melatonin receptor ligands in recent years. Ramelteon, an agonist that acts solely on melatonin MT(1) and MT(2) receptors, is of particular interest, and preliminary research indicates that it holds considerable promise for clinical applications. Ramelteon has been shown to induce sleep initiation and maintenance in various animal models and in clinical trials. In chronic insomnia, ramelteon decreases sleep latency and increases total sleep time and sleep efficiency, without causing hangover, addiction or withdrawal effects. Ramelteon is thought to promote sleep by influencing homeostatic sleep signaling mediated by the suprachiasmatic nucleus. Although ramelteon's metabolism and pharmacokinetics differ from those of melatonin, its safety seems to be sufficient for short-term application. Its long-term effects remain to be determined.
褪黑素是一种参与昼夜节律系统调控的生物钟调节剂，以其促进睡眠的作用而闻名，这些作用包括缩短睡眠潜伏期和延长睡眠时间。由于其半衰期短，褪黑素不会产生不良副作用，并且其对各种睡眠问题的广泛适用性一直是众多科学研究的重点。然而，褪黑素尚未获得美国食品药品监督管理局（FDA）作为药物的监管批准，因为它可以作为食品补充剂自由销售。因此，近年来一直在积极寻找可申请专利的褪黑素受体配体。雷美替胺是一种仅作用于褪黑素MT(1)和MT(2)受体的激动剂，特别受关注，初步研究表明它在临床应用方面有很大前景。在各种动物模型和临床试验中，雷美替胺已被证明能诱导睡眠起始和维持。在慢性失眠症中，雷美替胺可缩短睡眠潜伏期，增加总睡眠时间和睡眠效率，且不会引起宿醉、成瘾或戒断效应。雷美替胺被认为是通过影响视交叉上核介导的稳态睡眠信号来促进睡眠的。尽管雷美替胺的代谢和药代动力学与褪黑素不同，但其安全性似乎足以支持短期应用。其长期影响仍有待确定。
