Vilazodone shows an IC ₅₀ of 0.2 nM at the human 5-HT ₁ A receptor and 0.5 nM for the SERT. Vilazodone preferentially binds to the high agonist affinity state of human 5-HT ₁ A?receptors, and it displays high affinity (pK _i ≥9.3) for human recombinant and rat, guinea pig, mouse, and marmoset native tissue 5-HT _1A receptors.Vilazodone acts as a high efficacy partial agonist at 5-HT ₁ A?receptors. In [ ³⁵ S]GTPγS binding studies in Sf9 cells expressing h5-HT ₁ A?receptors, a single concentration of Vilazodone (100nM) increases basal binding by approximately 70% of that produced by the full 5-HT ₁ A?receptor agonist, 8‐OH‐PIPAT. In [ ³⁵ S]GTPγS binding studies in rat hippocampal membranes, Vilazodone acts as a potent 5‐HT _1A receptor partial agonist with a pEC ₅₀ of 8.1 and an intrinsic activity of 0.61. Vilazodone acts as a potent 5‐HT reuptake inhibitor in rat and guinea pig cortex. In LLCPK cells expressing human SERT, whereby vilazodone inhibits [ ³ H]5‐HT uptake with a pIC ₅₀ of 8.8.

Vilazodone (intraperitoneal injection; 3 mg/kg ; single dose) produces increases in extracellular levels of 5‐HT in both the frontal cortex (FC) and ventral hippocampus (vHipp) of rats in vivo?microdialysis studies. Maximum increases are observed at 3 mg/kg and reaches 527% and 558% of preinjection baseline values in the FC and vHipp, respectively. Vilazodone (oral gavage ;55 mg/kg ; single dose) inhibits stress‐induced vocalizations in the rat ultrasonic vocalizations test at 120 and 210 min post dose.