NS3623 is an activator of human ether-a-go-go-related gene (hERG1/K_V11.1) potassium channels. NS3623 activates the IKr and Ito currents and has antiarrhythmic effect. NS3623 has a dual mode of action, being an inhibitor of hERG1 channels^[1][2][3]. In Vitro: In isolated canine cardiomyocytes, application of NS3623 (5 μM) greatly increases the size of the tail current confirming previous studies demonstrating this drug increased IKr. The effect of NS3623 on IKr recorded from cells kept in culture is evaluated. After 48 h, the magnitude of IKr is greatly reduced compared to freshly isolated cells. Peak IKr tail currents are 0.47 ± 0.08 pA/pF in freshly isolated myocytes and 0.28 ± 0.06 pA/pF in 2 day cultured myocytes. Application of NS3623 increases IKr in cultured Mid cells. Analysis of the current-voltage (I-V) relation of IKr tail current showed that NS3623 increased current density in both 1 day and 2 day cultured Mid cells. On a percentage basis, NS3623 increases IKr tail currents (at +50 mV activating pulse) by 60% in normal Mid cells, and 68% in 48 h cultured cells^[3]. In Vivo: NS3623 (30 mg/kg; i.v.; lasting for 3 minutes) shortens the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs^[1].
NS3623 (50 mg/kg) shortenes the QT interval by 30 +/- 6% in conscious guinea pigs. NS3623 (50 mg/kg) immediately decreases the QTcF interval and remains significantly shortened for approximately 30 minutes^[1].