Centro di Neurofarmacologia e Centro di Eccellenza per Malattie Neurodegenerative, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di MIlano, Italy.
Eur Neuropsychopharmacol. 2012;22 Suppl 3:S482-6. doi: 10.1016/j.euroneuro.2012.06.016. Epub 2012 Aug 4.
Agomelatine is a novel and clinically effective antidepressant drug with melatonergic (MT1/MT2) agonist and 5-HT(2C) receptor antagonist properties. Both receptorial components are widely expressed in the central nervous system and it seems that this compound could act synergistically on both the melatonergic and the 5-HT(2C) receptors. In this review we will briefly summarize the preclinical evidence suggesting that the molecular-cellular effects of agomelatine and in turn its antidepressant activity are the result of a synergistic action between its agonism at MT1/MT2 and antagonism at 5-HT(2C) receptors. The antidepressant properties of agomelatine related to its effect on neurogenesis, cell survival, brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeleton associated protein (Arc) and stress-induced glutamate release, appear to be due to this synergistic action. Compared with traditional antidepressants which also affect these parameters, agomelatine is the only one able to resynchronize these effectors at distinct levels, circuital and intracellular. This suggests that agomelatine effects in restoring circadian rhythms and relieving depressive symptoms result from a synergistic interaction between melatonergic and serotonergic receptors.
阿戈美拉汀是一种新型的、具有临床疗效的抗抑郁药，具有褪黑素能（MT1/MT2）激动剂和 5-HT（2C）受体拮抗剂的特性。这两种受体成分在中枢神经系统中广泛表达，似乎这种化合物可以在褪黑素能和 5-HT（2C）受体上协同作用。在这篇综述中，我们将简要总结表明阿戈美拉汀的分子细胞作用及其抗抑郁活性是其对 MT1/MT2 的激动作用和对 5-HT（2C）受体的拮抗作用协同作用的结果的临床前证据。阿戈美拉汀与神经发生、细胞存活、脑源性神经营养因子（BDNF）、活性调节细胞骨架相关蛋白（Arc）和应激诱导的谷氨酸释放有关的抗抑郁特性似乎归因于这种协同作用。与也影响这些参数的传统抗抑郁药相比，阿戈美拉汀是唯一能够在不同水平、电路和细胞内使这些效应物重新同步的药物。这表明阿戈美拉汀在恢复昼夜节律和缓解抑郁症状方面的作用是褪黑素能和 5-羟色胺能受体协同相互作用的结果。
