AgoMelatine-D6

Uses

Agomelatine-d6 is labelled Agomelatine (A430000) which is a melatoninergic agonist and selective antagonist of 5-HT2C receptors, and has been shown to be active in several animal models of depression. Agomelatine (S20098) displayed pKi values of 6.4 and 6.2 at native (porcine) and cloned, human (h)5-hydroxytryptamine (5-HT)2C receptors, respectively.

Biological Activity

Agomelatine-d6 is intended for use as an internal standard for the quantification of agomelatine by GC- or LC-MS. Agomelatine is an agonist of melatonin (MT) receptors and a derivative of melatonin .1 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]GTPγS 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).2 Agomelatine (40 mg/kg) inhibits the penile erection response induced by the 5-HT2 agonist Ro 60-0175 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, indicating antidepressant-like and anxiolytic-like activity, in a transgenic neuroendocrine model of depression.3 It also increases the rate of readjustment to circadian activity cycles following an induced phase shift.

References

1.Poissonnier-Durieux, S., Ettaoussi, M., Pérès, B., et al.Synthesis of 3-phenylnaphthalenic derivatives as new selective MT2 melatoninergic ligandsBioorg. Med. Chem.16(18)8339-8348(2008) 2.Millan, M.J., Gobert, A., Lejeune, F., et al.The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathwaysJ. Pharmacol. Exp. Ther.306(3)954-964(2003) 3.Barden, N., Shink, E., Labbé, M., et al.Antidepressant action of agomelatine (S 20098) in a transgenic mouse modelProg. Neuropsychopharmacol. Biol. Psychiatry29(6)908-916(2005)