Institut de Recherches Internationales Servier, 6 Place des Pléiades, 92415 Courbevoie, Cedex, France.
Nat Rev Drug Discov. 2010 Aug;9(8):628-42. doi: 10.1038/nrd3140. Epub 2010 Jun 25.
Current management of major depression, a common and debilitating disorder with a high social and personal cost, is far from satisfactory. All available antidepressants act through monoaminergic mechanisms, so there is considerable interest in novel non-monoaminergic approaches for potentially improved treatment. One such strategy involves targeting melatonergic receptors, as melatonin has a key role in synchronizing circadian rhythms, which are known to be perturbed in depressed states. This article describes the discovery and development of agomelatine, which possesses both melatonergic agonist and complementary 5-hydroxytryptamine 2C (5-HT2C) antagonist properties. Following comprehensive pharmacological evaluation and extensive clinical trials, agomelatine (Valdoxan/Thymanax; Servier) was granted marketing authorization in 2009 for the treatment of major depression in Europe, thereby becoming the first approved antidepressant to incorporate a non-monoaminergic mechanism of action.
目前，对于常见且使人虚弱、具有高社会和个人成本的重度抑郁症的治疗还远远不能令人满意。所有现有的抗抑郁药都是通过单胺能机制起作用的，因此人们对潜在的改善治疗效果的新型非单胺能方法非常感兴趣。其中一种策略是针对褪黑素能受体，因为褪黑素在同步昼夜节律中起着关键作用，而众所周知，昼夜节律在抑郁状态下会受到干扰。本文描述了褪黑素激动剂和互补 5-羟色胺 2C（5-HT2C）拮抗剂阿戈美拉汀的发现和发展。经过全面的药理学评估和广泛的临床试验，阿戈美拉汀（ Valdoxan/Thymanax；Servier）于 2009 年在欧洲获得了治疗重度抑郁症的上市许可，成为第一个批准的包含非单胺能作用机制的抗抑郁药。
