Effect of vilazodone on 5-HT efflux and re-uptake in the guinea-pig dorsal raphe nucleus

The effect of vilazodone, a putative selective serotonin re-uptake inhibitor (SSRI) with 5-HT (5-hydroxytryptamine)1A receptor partial agonist activity, was investigated on 5-HT efflux and 5-HT re-uptake half life in the guinea-pig dorsal raphe nucleus, using in vitro fast cyclic voltammetry. The SSRI, fluoxetine, significantly increased 5-HT efflux. In contrast, vilazodone had no effect on 5-HT efflux at 100 nM but significantly decreased 5-HT efflux at 1 μM. Co-perfusion of 8-OH-DPAT (± 8-hydroxy-2-(di-n-propylamino)tetralin) with fluoxetine significantly attenuated the fluoxetine-induced increase in 5-HT efflux. Co-perfusion of WAY 100635 with vilazodone did not attenuate the effect of vilazodone alone. In addition, the re-uptake half life for 5-HT was significantly increased by both fluoxetine and vilazodone. In conclusion, we have demonstrated that vilazodone (100 nM, 1 μM), in the guinea-pig dorsal raphe nucleus, blocks the serotonin transporter but does not display 5-HT1A receptor agonism.