Agomelatine in Depressive Disorders: Its Novel Mechanisms of Action

Abstract

Disruptions in sleep and sleep-wake cycle regulation have been identified as one of the main causes for the pathophysiology of depressive disorders. The search has been on for the identification of an ideal antidepressant that could improve both sleep disturbances and depressive symptomatology. Melatonin, the major hormone of the pineal gland, has been shown to improve sleep and is involved in the regulation of the sleep-wake cycle. Identification of high concentrations of MT1 and MT2 melatonergic receptors in the suprachiasmatic nucleus of the anterior hypothalamus, the structure concerned with regulation of circadian rhythms and sleep-wake cycles, has led to the development of melatonergic agonists with greater potency and longer durations of action. Agomelatine is one such melatonergic agonist that acts specifically on MT1/MT2 melatonergic receptors and at the same time exhibits 5-HT2C antagonism, a property that is utilized by current antidepressants that are in clinical use. Agomelatine has been shown to be effective in a number of animal models of depression. Clinical studies undertaken on patients with major depression, bipolar disorders, seasonal affective disorder, and generalized anxiety disorder have all shown that agomelatine is also very effective in ameliorating depressive symptoms and manifesting early onset of action with a good tolerability and safety profile. It improved sleep efficiency and also resynchronized the disrupted circadian rhythms. Hence, the melatonergic modulation by agomelatine is suggested as one of the mechanisms for its antidepressant effect. Agomelatine's action on dendritic neurogenesis in animal models of depression is also identified as yet another action.

The Beneficial Effects of Agomelatine in Experimental Model of Sepsis Related Acute Kidney Injury

“…[33] The effect of agomelatine on inflammation was studied by Molteni et al [34] Pro-inflammatory cytokines were found to be reduced in rats treated with agomelatine, a finding similar to that of the present study. The authors reported that agomelatine modified the expression of enzymes involved in the kynurenine pathway.…”

Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration

“…High concentrations of melatonin in an exposure-timing-dependent manner (104) and at physiologic concentration, particularly through MT 1 receptors in the SVZ, have a modulatory effect on neural stem cell proliferation and differentiation (86). Recent studies have identified functions in neurogenesis for MT 1 and MT 2 agonists, including agomelatine (105,106), buspirone in combination with melatonin in major depressive disorder (107), and Nacetylserotonin, an intermediate of melatonin synthesis (108). Some evidence shows that a combination of melatonin and physical exercise enhances neurogenesis and neural survival (109) and some melatonin-receptor agonists promote proliferation in the dentate gyrus (110).…”

Agomelatine in the Treatment of Anxiety and Depressive Disorders in Patients With Ischemic Heart Disease

“…Некоторые исследования показали положи-тельные эффекты мелатонина для лечения нарушений сна [46][47][48], но применение мелатонина ограничено его низкой биодоступностью. На сегодняшний день аго-мелатин имеют самую большую клиническую базу из всех синтетических агонистов MT1 и MT2 мелатони-новых рецепторов.…”