Vilazodone HCl

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. ^[1]

Vilazodone selectively enhances serotonergic output in the prefrontal cortex of rats. Vilazodone demonstrates anxiolytic efficacy through Behavioral evaluations in the ultrasonic vocalization model of anxiety in rats. Vilazodone also shows efficacy but at a single dose only in the forced swim test (a putative model of depression). ^[1] Vilazodone (1-10 mg/kg p.o.) dose-dependently displaces in vivo [3H]DASB (N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine) binding from rat cortex and hippocampus, indicating that vilazodone occupies 5-HT transporters in vivo. Vilazodone (10 mg/kg p.o.) is demonstrated to cause a 2-fold increase in extracellular 5-HT but no change in noradrenaline or dopamine levels in frontal cortex of freely moving rats. ^[2] Vilazodone affects stress potentiation of startle at doses above 5 mg/kg in rats. Vilazodone increases stress elevation of startle at 10 mg/kg in rats. Vilazodone (20 and 40 mg/kg) blocked stress potentiation of startle in rats. Vilazodone increases stress elevation of startle at all doses in rats. ^[3] vilazodone has no effect on 5-HT efflux at 100 nM but significantly decreases 5-HT efflux at 1 mM in the guinea-pig dorsal raphe nucleus. Vilazodone significantly increases the re-uptake half life for 5-HT in the guinea-pig dorsal raphe nucleus. ^[4]