NS3623 is an activator of human ether-a-go-go-related gene (hERG) potassium channels with a dual mode of action, also acting as an inhibitor of hERG1 channels. It activates the IKr and Ito currents and exhibits an antiarrhythmic effect.

Administering NS3623 (5 μM) significantly enhances the tail current magnitude in isolated canine cardiomyocytes, corroborating earlier evidence that this compound augments IKr. Specifically, NS3623 boosts IKr tail currents by 60% in normal Mid cells and by 68% in cells cultured for 48 hours, at a +50 mV activating pulse. Furthermore, although the baseline IKr in cells cultured for 48 hours markedly declines compared to freshly isolated cells—from 0.47 ± 0.08 pA/pF to 0.28 ± 0.06 pA/pF—NS3623 application elevates IKr in these cultured Mid cells. An analysis of the current-voltage (I-V) relationship for IKr tail current reveals that NS3623 increases current density in Mid cells cultured for both one and two days.

NS3623 (30 mg/kg; i.v.; lasting for 3 minutes) shortens the corrected QT interval by 25 ± 4% in anaesthetized guinea pigs. At 50 mg/kg, NS3623 immediately reduces the QTcF interval and remains significantly shortened for approximately 30 minutes, also shortening the QT interval by 30 ± 6% in conscious guinea pigs [1].