Agomelatine

Agomelatine is an agonist of melatonin (MT) receptors and a derivative of melatonin (Item No. 14427).{53599} It binds to MT1 and MT2 receptors (Kis = 0.14 and 0.41 nM, respectively) and has an EC50 value of 0.1 nM in a [35S]GTP?S binding assay using CHO cells expressing MT2 receptors. Agomelatine is also an antagonist of the serotonin (5-HT) receptor subtypes 5-HT2B and 5-HT2C (Kis = 0.26 and 0.71 nM, respectively, for the human receptors).{16799} Agomelatine (40 mg/kg) inhibits the penile erection response induced by the 5-HT2 agonist Ro 60-0175 (Item No. 29500) in rats. It also increases extracellular levels of noradrenaline and dopamine in the frontal cortex of freely moving rats when administered at doses ranging from 20 to 80 mg/kg. Agomelatine (10 mg/kg) reduces immobility time in the forced swim test and increases the amount of time spent in the open arms of the elevated plus maze in mice, indicating antidepressant-like and anxiolytic-like activity, in a transgenic neuroendocrine model of depression.{53600} It also increases the rate of readjustment to circadian activity cycles following an induced phase shift.