Agomelatine and S 21517 have moderately high affinities for 5-HT
2C
receptors (
K
i
= 0.21 μM and 0.13 μM, respectively). The metabolite 3-Hydroxy agomelatine (S 21540) has a 10-fold lower affinity (
K
i
= 1.8 μM). Agomelatine, S 21517 and 3-Hydroxy agomelatine (10
-7
-10
-4
M) are antagonists at 5-HT
2C
receptors, with a rank order of efficacy as follows: S 21517>Agomelatine>3-Hydroxy agomelatine.
Increasing doses (from 1.25 to 40 mg/kg, intraperitoneal injection) of 3-Hydroxy agomelatine (S 21540) does not affect the penile erections induced by mCPP and Ro 60-0175 in Wistar rat.
