Résumés
Résumé
Divers axes de recherche ont été suivis pour obtenir de nouveaux traitements de la dépression plus efficaces, mieux tolérés et d’action plus rapide. Parmi ces axes de recherche, la mélatonine, synchronisateur endogène des rythmes biologiques chez les mammifères, suscite un intérêt croissant dans la mesure où la désorganisation des rythmes circadiens est caractéristique d’un grand nombre de troubles de l’humeur. L’agomélatine est un antidépresseur qui se distingue par des propriétés agonistes pour les récepteurs mélatoninergiques (MT1 et MT2) ; ses propriétés agonistes ont été confirmées lors d’études in vivo, l’agomélatine améliorant les perturbations des rythmes circadiens observés dans différents modèles animaux. La propriété antidépressive de l’agomélatine a été mise en évidence dans plusieurs modèles animaux validés, dont les tests de la nage forcée, de la résignation acquise ou du stress chronique modéré. De façon tout à fait intéressante, l’activité antidépressive de l’agomélatine ne repose pas uniquement sur une action chronobiotique : en fait, l’agomélatine présente une activité antagoniste sur les récepteurs 5-HT2C, et ce aux doses antidépressives. Par ailleurs, l’absence d’affinité de l’agomélatine vis-à-vis d’un large éventail de récepteurs lui confère un excellent profil de sécurité, particulièrement avantageux par rapport aux antidépresseurs déjà sur le marché (pas de désordres gastro-intestinaux ni de perturbations de la fonction sexuelle ou du sommeil). L’agomélatine inaugure donc un nouveau concept dans le traitement de la dépression.
Summary
There are now many potentials for the development of more effective, better tolerated, and more rapidly acting antidepressants acting in association and/or beyond the monoamine hypothesis. One of these possibilities is the development of antidepressant drugs with melatonin agonist property. This holds much promise since various affective disorders, including depression, are characterized by abnormal patterns of circadian rhythms. In line with this, the melatoninergic agonist properties of agomelatine, an antidepressant with proven clinical efficacy, may represent a new concept for the treatment of depression. By way of behavioral studies in rodents, it has been shown that administration of agomelatine can mimic the action of melatonin in the synchronization of circadian rhythm patterns. Interest in agomelatine has increased in recent times due to its prospective use as a novel antidepressant agent, as demonstrated in a number of animal studies using well-validated animal models of depression (including the forced swimming test, the learned helplessness, the chronic mild stress). Interestingly, the melatoninergic agonist property of agomelatine may not, alone, be sufficient to sustain its clear antidepressant-like activity. Recent results from receptor binding and in vivo studies gave support to the notion that agomelatine’s effects are also mediated via its function as a competitive antagonist at the 5-HT2C receptor. Finally, thanks to its absence of binding with a broad range of receptors and enzymes, agomelatine is particularly safe and devoid of all the deleterious effects reported with tricyclics and SSRIs.
Parties annexes
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