Cardinali Daniel P, Pandi-Perumal Seithikurippu R, Srinivasan Venkataramanujan, Spence D Warren, Trakht Ilya
a Departamento de Fisiología, Facultad de Medicina, UBA Paraguay 2155, 1121 Buenos Aires, Argentina.
b Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street - Rm BB813, NY 10032, USA.
Expert Rev Endocrinol Metab. 2008 Mar;3(2):269-279. doi: 10.1586/17446651.3.2.269.
Melatonin, a hormone secreted by the pineal gland, has been successfully employed to improve sleep in both normal patients and insomniacs, and for the treatment of circadian rhythm sleep disorders. Melatonergic MT and MT receptors exist in high concentrations in the suprachiasmatic nucleus of the hypothalamus and have been shown to be instrumental for the sleep-promoting and circadian rhythm-regulating effects of melatonin. A lack of consistency among reports on the therapeutic efficacy of melatonin has been attributed to differences in melatonin's bioavailability and the short half-life of the hormone. In view of the need for longer acting melatonergic agonists that improve sleep efficiency without causing drug abuse or dependency, ramelteon (Rozerem™, Takeda) was developed. Ramelteon, which acts via MT/MT melatonergic agonism, has been found clinically effective for improving total sleep time and sleep efficiency in insomniacs. Agomelatine (Valdoxan™, Servier) is another MT/MT melatonergic agonist that also displays antagonist activity at 5-HT serotonin receptors. Agomelatine has been found effective in treating depression and sleep disorders in patients with major depressive disorder. A slow-release preparation of melatonin (Circadin™, Neurim) has been shown to be effective in treating sleep disorders in the elderly population.
褪黑素是一种由松果体分泌的激素，已成功用于改善正常患者和失眠症患者的睡眠，以及治疗昼夜节律性睡眠障碍。褪黑素能MT和MT受体在下丘脑视交叉上核中高浓度存在，并已证明对褪黑素的促睡眠和昼夜节律调节作用至关重要。关于褪黑素治疗效果的报道缺乏一致性，这归因于褪黑素生物利用度的差异以及该激素的短半衰期。鉴于需要长效的褪黑素能激动剂来提高睡眠效率而不引起药物滥用或依赖，研发了雷美替胺（Rozerem™，武田公司）。雷美替胺通过MT/MT褪黑素能激动作用发挥作用，临床上已发现其对改善失眠症患者的总睡眠时间和睡眠效率有效。阿戈美拉汀（Valdoxan™，施维雅公司）是另一种MT/MT褪黑素能激动剂，它在5-羟色胺受体上也表现出拮抗活性。已发现阿戈美拉汀对治疗重度抑郁症患者的抑郁症和睡眠障碍有效。一种褪黑素缓释制剂（Circadin™，Neurim公司）已证明对治疗老年人群的睡眠障碍有效。
