In vitro activity: Vilazodone demonstrates an IC50 of 0.2 nM at the human 5-HT1A receptor and 0.5 nM for the SERT. Vilazodone displays high affinity (pKi ≥ 9.3) for human recombinant and rat, guinea pig, mouse, and marmoset native tissue 5-HT1A receptors.

Cell Assay: Administration of 5-HT1A receptor agonists produce a characteristic behavioral syndrome that includes changes in posture, hind limb reduction, head weaving, tremors, forepaw treading, and straub tail. In the rat ultrasonic vocalizations test, stress-induced vocalizations are inhibited by Vilazodone (55 mg/kg po) at 120 and 210 min post dose. Vilazodone (20-40 mg/kg ip), administered acutely or prophylactically (1 week prior to behavioral testing), attenuated stress induces potentiated startle but has no effect on stress potentiated anxiety response in the elevated plus maze. Interestingly, a lower dose of 10 mg/kg of Vilazodone has the opposite effect in the startle response, indicating a somewhat unexplained bidirectional effect, and all doses produce a potentiation of the startle-induced stress response possibly suggestive of an anxiogenic-like response[1]. Vilazodone also represents another option for the treatment of MDD.