Potent Inhibition of hERG Channels by the Over-the-Counter Antidiarrheal Agent Loperamide

JACC. Clinical Electrophysiology
Michael G KleinMori J Krantz

Abstract

The aim of this study was to determine the in vitro electrophysiological properties of loperamide. The authors' hypothesis was that loperamide is a potent blocker of the current carried by the human ether-à-go-go-related gene (hERG) potassium channel. Loperamide is a peripherally-acting μ-opioid agonist available worldwide as an over-the-counter treatment for diarrhea. Like most opioids, it is not currently known to be proarrhythmic. Recent cases of torsade de pointes in association with high-dose loperamide raise concern given its structural similarity to methadone, another synthetic opioid with an established arrhythmia risk. Effects of loperamide on blockade of the hERG potassium channel ion current were assessed in Chinese Hamster Ovary (CHO) cells stably expressing hERG to elucidate current amplitude and kinetics. The concentration required to produce 50% inhibition of hERG current was assessed from the amplitude of tail currents and the impact on action potential duration was assessed in isolated swine ventricular cardiomyocytes. The 50% inhibitory concentration for loperamide inhibition of hERG ionic tail currents was approximately 40 nmol/l. In current-voltage measurements, loperamide reduced steady and tail currents an...Continue Reading

Citations

May 31, 2018·Journal of Cardiovascular Electrophysiology·Asim AhmedEric N Prystowsky
Jun 21, 2019·Journal of Forensic Sciences·John W Powell, Susan Erin Presnell
Jan 7, 2020·International Anesthesiology Clinics·C James WatsonMichael Ganetsky
Jun 3, 2017·Journal of Addiction Medicine·Raphael J LeoKelly S Jaziri
May 13, 2017·Natural Product Reports·Jadel M KratzJudith M Rollinger
Aug 28, 2020·Journal of Community Hospital Internal Medicine Perspectives·Zain AliWaqas Ullah
Nov 22, 2020·Letters in Applied Microbiology·O M BarrientosS Guzmán-Beltrán
Aug 7, 2021·The Journal of General Physiology·Alexandre G VougaBrad S Rothberg
Aug 11, 2021·British Journal of Clinical Pharmacology·Talip E ErogluUNKNOWN ESCAPE-NET Investigators
Apr 14, 2020·American Journal of Therapeutics·Raunak Mohan NairRoy Chung

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