Agomelatine, the first melatonergic antidepressant: discovery, characterization and development.
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.
de Bodinat
Christian
C
Institut de Recherches Internationales Servier, 6 Place des Pléiades, 92415 Courbevoie, Cedex, France.
Guardiola-Lemaitre
Béatrice
B
Mocaër
Elisabeth
E
Renard
Pierre
P
Muñoz
Carmen
C
Millan
Mark J
MJ
D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002940:Circadian Rhythm; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D008550:Melatonin / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D009281:Naphthalenes
D000081:Acetamides; D000928:Antidepressive Agents; D008550:Melatonin; D058830:Serotonin 5-HT2 Receptor Antagonists; C084711:agomelatine; D009281:Naphthalenes