Melatonergic药物在临床实践中。

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Hardeland R, Poeggeler B, Srinivasan V, Trakht我,Pandi-Perumal SR, Cardinali DP

Melatonergic药物在临床实践中。

Arzneimittelforschung。2008; 58 (1): 1 - 10。doi: 10.1055 / s - 0031 - 1296459。

PubMed ID

18368944 (在PubMed

]

文摘

褪黑激素(ca 73-31-4)催眠和睡眠/唤醒节奏调节特性。这些睡眠促进行动,已经明显在健康的人类,已经发现有用的科目遭受昼夜节律睡眠障碍(CRSD)像睡眠相位后移症候群(dsp)、时差和轮班工作睡眠障碍。低夜间褪黑激素的生产和分泌已经记录在老年失眠症患者,和外源性褪黑素已被证明是有益的在治疗这些患者的睡眠障碍。相比一些促进睡眠的化合物通常规定,如苯二氮卓类和z-drugs(唑吡坦和zopiclon属于后者的),临床价值的褪黑激素有几个优点:它不会导致宿醉和戒断效果和没有任何上瘾的潜力。然而,最近的荟萃分析显示,褪黑激素是不够有效的治疗最主要的睡眠障碍。有限的一些原因功效的天然激素相关的半衰期极短循环,和睡眠,维护也由下游主要melatonergic行动的机制。因此,迫切需要发展的褪黑激素受体受体激动剂有更长的半衰期,这可能适合一个成功治疗失眠。此类需求满足ramelteon (ca 196597-26-9),具有高亲和力的褪黑激素受体MT1是出现在昼夜起搏器,视交叉上核(SCN)。Ramelteon也明显比褪黑激素更长的半衰期。这种新药已成功用于治疗老年失眠症患者没有任何不良反应报道,并承诺治疗原发性失眠患者以及那些患有CRSD。 Since sleep disturbances constitute the most prevalent symptoms of various forms of depression, the need for the development of an ideal antidepressant was felt, which would both improve sleep and mitigate depressive symptoms. Since most of the currently used antidepressants, including the selective serotonin re-uptake inhibitors worsen the sleep disturbances of depressive patients, another novel melatonergic drug, agomelatine (CAS 138112-76-2), holds some promise because of its particular combination of actions: it has a high affinity for MT1 and MT2 receptors in the SCN, but it acts additionally as a 5-HT(2C) antagonist [5-hydroxytryptamine (serotonin) receptor 2C antagonist]. The latter property, which is decisive for the antidepressive action, would not favor but potentially antagonize sleep, but this is overcome during night by the melatonergic, sleep-promoting effect. This drug has been found beneficial in treating patients with major depressive and seasonal affective disorders. Unlike the other antidepressants, agomelatine improves both sleep and clinical symptoms of depressive illness and does not have any of the side effects on sleep seen with other compounds in use. This property seems to be of particular value because of the aggravating effects of disturbed sleep in the development of depressive symptoms. Based on these facts, agomelatine seems to be a drug of superior efficacy with a promising future in the treatment of depressive disorders. However, long-term safety studies are required for both ramelteon and agomelatine, with a consideration of the pharmacology of their metabolites, their effects on redox metabolism, and of eventual undesired melatonergic effects, e. g., on reproductive functions. According to current data, both compounds seem to be safe during short-term treatment

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药物

Agomelatine