Agomelatine (S20098)

Agomelatine completely normalizes stress-affected cell survival and partly reverses reduced doublecortin expression in the hippocampus of rats subjected to chronic footshock stress. ^[1]

Agomelatine is effective in reversing the transgenic mouse behavioural changes noted in the Porsolt forced swim test as well as in the elevated plus maze. Agomelatine also markedly accelerates readjustment of circadian cycles of temperature and activity following an induced phase shift. ^[2] Agomelatine enhances cell proliferation and neurogenesis in the ventral hippocampus (VH) of adult rats, a region pertinent to mood disorders. Agomelatine increases the ratio of mature vs immature neurons and enhances neurite outgrowth of granular cells in adult rats, suggesting an acceleration of maturation. Agomelatine also activates several cellular signals (extracellular signal-regulated kinase1/2, protein kinase B, and glycogen synthase kinase 3beta) known to be modulated by antidepressants and implicated in the control of proliferation/survival. ^[3] Agomelatine enhances the time devoted to active social interaction in unfamiliar pairs of rats exposed to a novel environment. ^[4] Agomelatine increases cell proliferation and neurogenesis in the ventral dentate gyrus of rats, a region notably implicated in response to emotion, which is consistent with the antidepressant-anxiolytic properties of Agomelatine. Agomelatine increases survival of newly formed neurons in the entire dentate gyrus of rats. ^[5]