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

摘要

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, soestalot, with an ester linkage introduced to the molecule to shorten half-life. Their hypothesis was that soestalot, but not the acid metabolite, would inhibit the hERG potassium current. Whole-cell, voltage-damp experiments were performed on cells expressing hERG. Soestatot inhibited outward I-hERG tail current density in a manner similar to conventional sotatot. Additionally, soestalot right shifted the voltage dependence of activation. These results warrant further assessment of soestalot as a short-acting, Class III antiarrhythmic drug. (C) 2020 by the American College of Cardiology Foundation.