Inhibitory Effectiveness in Delayed-Rectifier Potassium Current Caused by Vortioxetine, Known to Be a Novel Antidepressant

Vortioxetine (VOR) is recognized to exert antidepressant actions. However, whether this drug modifies ionic currents in excitable cells remains unclear. The aim of this study was to explore the electrophysiological effects of VOR and other related compounds in pituitary GH(3) cells and in Neuro-2a cells. VOR suppressed the delayed-rectifier K(+) current (I(K(DR))) in a concentration-, time-, and state-dependent manner. Effective IC(50) values needed to inhibit peak and sustained I(K(DR)) were computed to be 31.2 and 8.5 μM, respectively, while the K(D) value estimated from minimal binding scheme was 7.9 μM. Cell exposure to serotonin (10 μM) alone failed to alter I(K(DR)), while fluoxetine (10 μM), a compound structurally similar to VOR, mildly suppressed current amplitude. In continued presence of VOR, neither further addition of propranolol nor risperidone reversed VOR-mediated inhibition of I(K(DR)). Increasing VOR concentration not only depressed I(K(DR)) conductance but also shifted toward the hyperpolarized potential. As the VOR concentration was raised, the recovery of I(K(DR)) block became slowed. The I(K(DR)) activated by a downsloping ramp was suppressed by its presence. The inhibition of I(K(DR)) by a train pulse was enhanced during exposure to VOR. In Neuro-2a cells, this drug decreased I(K(DR)). Overall, inhibitory effects of VOR on ionic currents might constitute another underlying mechanism of its actions.