CS-2407

YL0919 inhibits the uptake of [ ³ H]-5-HT into rat cerebral cortical synaptosomes and HEK293 cells stably expressing hSERT with IC ₅₀ values of 1.78 nM and 1.93,respectively.YL0919 (0.01 nM-10 μM) concentration-dependently inhibits forskolin-stimulated cAMP formation,  exerts a concentration-dependent inhibitory effect on cAMP formation with an IC ₅₀ of approximately 23.9 nM. And in antagonism studies, WAY-100635 prevents YL0919-mediated inhibition of forskolin-stimulated cAMP formation. YL0919 shows affinities to rat 5-HT1A receptors, SERTs, NETs, and DATs, it binds to 5-HT1A receptor, serotonin transporter (SERT) with high affinity (K _i =0.19 and 0.72 nM, respectively), but its affinity to NET and DAT are low, blocking [ ³ H]nisoxetine and [ ³ H]win35428 binding with Ki values of 650 nM and 2652 nM respectively.

YL0919 (oral administration; 1.25 or 5 mg/kg; 4 weeks) and fluoxetine (10 mg/kg) reverses the inhibition of locomotor activity in CUS rats.YL0919 (oral administration; 1.25, 2.5, and 5 mg/kg; 4 weeks) significantly reduces the immobility time in TST in mcie FST in mice. Besides, YL0919 displays no effect on the locomotor activity in a separate OFT. Furthermore, the antidepressant-like effect of YL0919 in TST and FST is completely bunted by coadministration with WAY-100635.