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Agomelatine, an innovative pharmacological response to unmet needsINSERM U675, IFR02, Faculté de Médecine Xavier Bichat/Université Paris, Paris, France
INSERM U675, IFR02, Faculté de Médecine Xavier Bichat/Université Paris, Paris, France; Service de Psychiatrie, Hôpital Louis Mourier/AP-HP, Colombes, France philip.gorwood{at}lmr.ap-hop-paris.fr Abstract Most of the available antidepressants, with different pharmacological profiles, such as inhibitors of serotonin reuptake (SSRIs) or norepinephrine reuptake (NRIs) or both (SNRIs), have limitations leading some patients to drop out of treatment. Another direction of research has therefore been undertaken, based initially on the fact that affective disorders are most often characterized by abnormal patterns of circadian rhythms. This consideration has led to the synthesis of agomelatine, a novel antidepressant combining melatonergic MT1 and MT2 agonism and serotonergic 5-HT2C antagonism. The antidepressant effects of agomelatine have been investigated in different animal models, including chronic mild stress, forced swimming, learned helplessness and psychosocial stress. All studies reported an antidepressant-like effect of agomelatine. A resynchronizing activity of agomelatine was seen in animal models for delayed sleep phase syndrome and in several original models of circadian disturbance, such as rodents infected by trypanosome or old hamsters. This activity of agomelatine on circadian rhythms was further confirmed in humans. Furthermore, several randomized, double-blind, placebo-controlled and comparator-controlled studies of agomelatine in the treatment of major depressive disorder indicate that agomelatine is effective and well tolerated.
Key Words: agomelatine • antidepressant • circadian rhythms • melatonin • review
Journal of Psychopharmacology, Vol. 22, No. 7 suppl,
4-8 (2008) |
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