Wf-516 is a 5-HT reuptake inhibitor (Kis: 5 nM and 40 nM for 5-HT1A receptor and 5-HT2A receptor in humans, respectively), and with potent antidepressant activity.

5-HT2A receptor (human):40 nM (ki), 5-HT1A receptor (human):ki:5 nM

WF-516 exhibits high affinity for 5-HT1A receptors in the hippocampus and raphe nucleus of rats (Ki of 8.1 nM and 7.9 nM, respectively) [2].

Wf-516 (0.5 mg/kg, i.v.) does not alter the firing activity of 5-HT neurons but significantly inhibits the effect of 8-OHDPAT (a 5-HT autoreceptor agonist) by 70%. The suppression of DRN firing activity by LSD experienced a significant fourfold rightward shift in Wf-516 pretreated rats (ED50 = 32.4 ± 1.0 μg/kg) compared to controls (ED50 = 7.5 ± 1.2 μg/kg). Successive intravenous doses of Wf-516 (up to 10 mg/kg) prolong the effect of microiontophoretically applied 5-HT, achieving statistical significance at 7.5 mg/kg, with RT50 values increased by 53% and 75% at 7.5 mg/kg and 10 mg/kg, respectively. Oral administration of 30 mg/kg Wf-516 to 5,7-DHT-treated rats resulted in a significant decrease in hippocampal BPND, with no further decrease in the grooved nuclei; ED50 values were 5.3 mg/kg in the hippocampus and 4.2 mg/kg in the grooved nuclei.