Agomelatine

Class Melatonin receptor agonist
Chemistry

Acetamide

Routes of administration

Oral only

Absorption

Well absorbed (78%), with terrible bioavailability (less than 5%)

Solubility

pKa 15.6; minimally water-soluble

Distribution

VOD=30L/kg; 95% protein-bound

Metabolism

Hepatic metabolism by 7-O-demethylation and hydroxylation; all metabolites are inactive at MT receptors

Elimination

About 80% of the metabolites are eliminated in the urine, and the rest in the bile

Time course of action

Elimination half-life is about 2.3 hours; duration of activity is much longer

Target receptor

Melatonin MT1 and MT2 receptors, which are G-protein coupled receptors

Mechanism of action

Mechanism of action is thought to be related to the regulation of dopamine release by melatonin receptor activation (i.e. the efefct of agomelatine, as an MT1 and MT2 agonist, is to increase the concentration of dopamine).

Clinical effects

Both sedation and insomnia have been reported as side effects, but generally the incidence of side effects seems to be no greater than placebo

Literature reference

Zupancic et al (2006)

CICM details of understanding Not specifically listed in the CICM syllabus
Mentioned around Deranged Physiology
Related SAQs