In vitro activity: Dapoxetine not only reduces the peak amplitude of Kv4.3 currents but also accelerates the decay rate of current inactivation in a concentration-dependent manner. Dapoxetine decreases the integral of the Kv4.3 currents over the duration of a depolarizing pulse with an IC50 of 5.3 μM. Dapoxetine also causes a substantial acceleration in closed-state inactivation. Dapoxetine produces a significant use-dependent block, which is accompanied by a delayed recovery from inactivation of Kv4.3 currents. Dapoxetine decreases the peak amplitude of Kv1.5 currents and accelerates the decay rate of current inactivation in a concentration-dependent manner with an IC50 of 11.6 μM. Dapoxetine decreases the tail current amplitude and slows the deactivation process of Kv1.5, which results in a tail crossover phenomenon. Dapoxetine produces a use-dependent block of Kv1.5 at frequencies of 1 and 2 Hz and slowed the time course for recovery of inactivation. Dapoxetine also appears to be a useful adjunct to morphine, lowering the threshold for analgesia, although Dapoxetine itself has negligible analgesic activity. Dapoxetine is the D-enantiomer of LY 243917 and is 3.5 times more potent as a serotonin reuptake inhibitor than the L-enantiomer.