tcsc1471 Vortioxetine

Vortioxetine is a inhibitor of 5-HT_1A, 5-HT_1B, 5-HT_3A, 5-HT₇ receptor and SERT, with K_i values of 15 nM, 33 nM, 3.7 nM, 19 nM and 1.6 nM, respectively.

IC50 & Target: Ki: 15 nM (5-HT_1A); 33 nM (5-HT_1B); 3.7 nM (5-HT_3A); 19 nM (5-HT₇); 1.6 nM (SERT)_[1].

In Vitro: Vortioxetine (Compound 5m) is a multimodal serotonergic agent, inhibits 5-HT_1A, 5-HT_1B, 5-HT_3A, 5-HT₇ receptor and SERT with K_i values of 15 nM, 33 nM, 3.7 nM, 19 nM and 1.6 nM, respectively. Vortioxetine displays antagonistic properties at 5-HT_3A and 5-HT₇ receptors, partial agonist properties at 5-HT_1B receptors, agonistic properties at 5-HT_1A receptors, and potent inhibition of SERT_[1]. Vortioxetine is a partial h5-HT _1B receptor agonist with EC₅₀ of 460 nM and intrinsic activity of 22% using a whole-cell cAMP-based assay. Vortioxetine binds to the r5-HT ₇ receptor with a K_i value of 200 nM and is a functional antagonist at the r5-HT₇ receptor with an IC₅₀ of 2 μM in an in vitro whole-cell cAMP assay_[5].

In Vivo: Vortioxetine (Lu AA21004) occupies the r5-HT_1B receptor and rSERT (ED₅₀= 3.2 and 0.4 mg/kg, respectively) after subcutaneous administration and is a 5-HT₃ receptor antagonist_[6]. Vortioxetine significantly increases cell proliferation and cell survival and stimulates maturation of immature granule cells in the sub granular zone of the dentate gyrus of the hippocampus after 21 days of treatment_[3]. Vortioxetine does not cause cognitive or psychomotor impairment_[4].