Vilazodone

Vilazodone (EMD 68843; SB 659746A) is a potent, selective and orally active?serotonin?reuptake inhibitor (SSRI) and partial?5-HT₁A receptor agonist. Vilazodone exhibits antidepressant efficacy in vivo can be used for the research of major depressive disorder (MDD) and affective disorders^[1][2]. In Vitro: Vilazodone shows an IC₅₀ of 0.2 nM at the human 5-HT₁A receptor and 0.5 nM for the SERT. Vilazodone preferentially binds to the high agonist affinity state of human 5-HT₁A?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-HT₁A?receptors. In [³⁵S]GTPγS binding studies in Sf9 cells expressing h5-HT₁A?receptors, a single concentration of Vilazodone (100nM) increases basal binding by approximately 70% of that produced by the full 5-HT₁A?receptor agonist, 8-OH-PIPAT.
In [³⁵S]GTPγS binding studies in rat hippocampal membranes, Vilazodone acts as a potent 5-HT_1A?receptor partial agonist with a pEC₅₀?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 [³H]5-HT uptake with a pIC₅₀?of 8.8^[1].
In Vivo: 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^[2].
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^[2].