Agomelatine, the first melatonergic antidepressant: discovery, characterization and development

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.

Publication types

  • Review

MeSH terms

  • Acetamides / pharmacology*
  • Acetamides / therapeutic use
  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Circadian Rhythm
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Drug Design
  • Drug Discovery
  • Humans
  • Melatonin / metabolism
  • Serotonin 5-HT2 Receptor Antagonists


  • Acetamides
  • Antidepressive Agents
  • Serotonin 5-HT2 Receptor Antagonists
  • agomelatine
  • Melatonin