Wf-516

Wf-516 is an inhibitor of 5-HT reuptake, and an antagonist of 5-HT1A and 5-HT2A receptors, with K_i of 5 nM and 40 nM for 5-HT1A receptor and 5-HT2A receptor in humans, respectively, and has potent antidepressant activity. IC50 & Target: Ki: 5 nM (Human 5-HT1A receptor), 40 nM (Human 5-HT2A receptor)^[1] In Vitro: Wf-516 shows high affinity for 5-HT1A receptors in the hippocampus and raphe nucleus of rats with K_i of 8.1 nM and 7.9 nM, respectively^[2]. In Vivo: Wf-516 (0.5 mg/kg, i.v.) does not induce any change in the firing activity of 5-HT neurons, but significantly blocks the inhibitory effect of 8-OHDPAT (a 5-HT autoreceptor agonist) by 70%. A full dose-response relationship between the suppression of DRN firing activity and different doses of LSD shows a significant fourfold shift to the right in the Wf-516 pretreated rats (ED₅₀?=?32.4?±?1.0 μg/kg) as compared to controls (ED₅₀?=?7.5?±?1.2 μg/kg). After intravenous administration of successive doses of 1.25 mg/kg of Wf-516 (up to 10 mg/kg), the effect of microiontophoretically applied 5-HT is prolonged and reaches statistical significance at 7.5 mg/kg. At this dose, the RT₅₀ value is increased by 53% and, by 75% at the highest dose of 10 mg/kg of Wf-516 used^[1]. Oral administration of 30 mg/kg Wf-516 to these 5,7-DHT-treated rats induces a significant decrease of BPND in the hippocampus as compared with baseline, but no additional reduction of BPND is observed in the raphe nucleus. Oral ED₅₀ values for Wf-516 in the hippocampus and raphe nucleus are 5.3 mg/kg and 4.2 mg/kg, respectively^[2].