Table 4.

Pharmacodynamics of Commercially Available Melatonin Receptor Agonists

Parameter	Agomelatine51	Prolonged‐release melatonin52	Ramelteon59	Tasimelteon48, 58
Mechanism of action	MT1 and MT2 agonist; serotonin 5‐HT2C antagonist	MT1, MT2, and MT3 agonist	MT1, MT2, and selective MT3 agonist	MT1 and MT2 agonist
Receptor binding affinity (Ki values [nM])	MT1: 0.10 MT2: 0.12 5‐HT2C: 6.15	MT1: 0.081 MT2: 0.383	MT1: 0.014 MT2: 0.112	MT1: 0.304 MT2: 0.0692
Metabolite activity	Primary metabolites: (hydroxylated and demethylated agomelatine) inactive	Principal metabolite (6‐sulphatox‐y melatonin [aMT6s]) inactive	Four metabolites (M‐II, M‐IV, M‐I, and M‐III [in order of prevalence in human serum]); MT‐II active at MT1 (10% affinity of parent) and MT2 (20% affinity of parent compound), with systemic exposure 20‐ to 100‐fold higher than parent compound and mean terminal T1/2 of 2–5 hrs	Primary metabolites: M3, M9, M11, M12, M13, and M14; low binding affinity for MT1 and MT2 (< 1/10 of the binding affinity of the parent compound); low activity at melatonin receptors (at least 13‐fold less than parent compound); mean terminal elimination T1/2 of the main metabolites ranges from 1.3 ± 0.5–3.7 ± 2.2 hrs

T_1/2 = half‐life.