De Berardis Domenico, Marini Stefano, Fornaro Michele, Srinivasan Venkataramanujam, Iasevoli Felice, Tomasetti Carmine, Valchera Alessandro, Perna Giampaolo, Quera-Salva Maria-Antonia, Martinotti Giovanni, di Giannantonio Massimo
National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4 Teramo, Italy.
Int J Mol Sci. 2013 Jun 13;14(6):12458-83. doi: 10.3390/ijms140612458.
Melatonin exerts its actions through membrane MT1/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in "real world" clinical practice will be also discussed.
褪黑素通过膜MT1/MT2褪黑素受体发挥作用，这些受体属于由典型的七个跨膜结构域组成的G蛋白偶联受体超家族。MT1和MT2受体在身体的各种组织中单独或共同表达。越来越多的文献表明，褪黑素能神经系统可能参与情绪和焦虑障碍的病理生理学过程。事实上，抑郁症的一些核心症状在临床表现上显示出昼夜节律紊乱，如日间情绪和其他症状变化，或与昼夜节律系统功能密切相关，如睡眠-觉醒周期改变。此外，抑郁症患者的几种生物标志物的昼夜节律也出现了改变。因此，人们对开发具有生物钟调节作用（即治疗昼夜节律紊乱）的抗抑郁药很感兴趣。由于褪黑素具有生物钟调节作用，人们一直致力于开发阿戈美拉汀，一种具有褪黑素激动剂活性的抗抑郁药。本文综述了褪黑素能神经系统在情绪和焦虑障碍病理生理学中的作用以及阿戈美拉汀的临床特征。还将讨论阿戈美拉汀在“现实世界”临床实践中的意义。
