Agomelatine is an atypical antidepressant used to treat major depressive disorder. One review found that it is as effective as other antidepressants with similar discontinuation rates overall but less discontinuations due to side effects. Generic Valdoxan available with delivery to UK, AU, US from India. Agomelatine 25mg made by popular manufacturers.
Agomelatine is a synthetic melatonin analog initially evaluated for its chronobiotic effect. Later when its effect on serotonergic receptors were discovered, it was investigated as an antidepressant. It is an agonist at melatonergic MT1 and MT2 receptors and antagonist at serotonin 5HT2C receptor.
Many hypotheses (monoamine hypothesis, neurotropic hypothesis, etc.) have been proposed to explain the pathophysiology of major depression. Phase-shift hypothesis is one among them and postulates that phase delay in internal circadian rhythm can lead to depression. Stimulation of melatonergic (MT1 / MT2) receptors in suprachiasmatic nucleus of hypothalamus by agomelatine leads to the restoration of disturbed circadian rhythm. Hence it is referred to as ‘rhythm stabilizing antidepressant’. By virtue of its selective binding to serotonin 5HT2C receptors, agomelatine secondarily increases norepinephrine and dopamine levels. This property also accounts for its antidepressant activity. It does not have any action on adrenergic, cholinergic and histamine receptors.