Author + information
- Received April 1, 2020
- Revision received May 21, 2020
- Accepted May 23, 2020
- Published online July 20, 2020.
- Tyler Shugg, PharmD, PhDa,b,
- John C. Somberg, MDc,d,
- Janos Molnar, MDd,e and
- Brian R. Overholser, PharmDa,b,∗ ()
- aDepartment of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, Indiana
- bDivision of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana
- cDepartment of Medicine and Pharmacology, Rush University, Chicago, Illinois
- dAmerican Institute of Therapeutics, Lake Bluff, Illinois
- eDepartment of Medicine, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois
- ↵∗Address for correspondence:
Dr. Brian R. Overholser, Purdue University College of Pharmacy, Research Institute 2: Room 402, 950 West Walnut Street, Indianapolis, Indiana 46202.
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 IhERG 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.
This work was supported by a grant from Academic Pharmaceuticals Inc. (to Dr. Overholser). Dr. Somberg is the chief executive officer for Academic Pharmaceuticals; and has financial interest in intravenous soestalol. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received April 1, 2020.
- Revision received May 21, 2020.
- Accepted May 23, 2020.
- 2020 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.