Inhibition of Human Ether-A-Go-Go-Related Gene (hERG) Potassium Current by the Novel Sotalol Analogue, Soestalol

Abstract

The clinical utility of intravenous sotalol is limited due to an extended half-life combined with the potential to generate life-threatening arrhythmias. The authors developed a novel sotalol analogue, soestalol, with an ester linkage introduced to the molecule to shorten half-life. Their hypothesis was that soestalol, but not the acid metabolite, would inhibit the hERG potassium current. Whole-cell, voltage-clamp experiments were performed on cells expressing hERG. Soestalol inhibited outward I_hERG tail current density in a manner similar to conventional sotalol. Additionally, soestalol right shifted the voltage dependence of activation. These results warrant further assessment of soestalol as a short-acting, Class III antiarrhythmic drug.

Keywords: I(Kr); hERG; soestalol; sotalol; torsades de pointes.