MT1 and MT2 Receptors agonist; 5-HT Receptor antagonist
Form:
Free Base
REVIEW 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 MT 1 and MT 2 receptors and antagonist at serotonin 5HT 2C 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 (MT 1 / MT 2 ) 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 5HT 2C 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.
REFERENCES
[1]
Tabeeva GR, Sergeev AV, Gromova SA (2011). [Possibilities of preventive treatment of migraine with the MT1- and MT2 agonist and 5-HT2c receptor antagonist agomelatin (valdoxan)]. Zh Nevrol Psikhiatr Im S S Korsakova. 111(9):32-6. PMID 22027667.
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