Block of the rapid component of the delayed rectifier potassium current by the prokinetic agent cisapride underlies drug-related lengthening of the QT interval

Circulation
Benoît DroletJacques Turgeon

Abstract

Lengthening of the QT interval and torsades de pointes resulting in cardiac arrests and deaths have been noticed during treatment with cisapride, a newly developed gastrointestinal prokinetic agent. The rapid (I[Kr]) and slow (I[Ks]) components of the delayed rectifier current (I[K]) are candidate ionic currents to explain cisapride-related toxicity because of their role in repolarization of cardiac ventricular myocytes. Our objectives were to (1) characterize effects of cisapride on two major time-dependent outward potassium currents involved in the repolarization of cardiac ventricular myocytes, I(Kr) and I(Ks), and (2) determine action potential-prolonging effects of cisapride on isolated hearts. A first set of experiments was performed in isolated guinea pig ventricular myocytes with the whole-cell configuration of the patch-clamp technique. Cells were held at -40 mV while time-dependent outward currents were elicited by depolarizing pulses lasting either 250 ms (I[K250]) or 5000 ms (I[K5000]). Effects of cisapride on the I(Kr) component were assessed by measurement of time-dependent activating currents elicited by short pulses (250 ms; I[K250]) to low depolarizing potentials (-20, -10, and 0 mV). Time-dependent activating ...Continue Reading

References

Feb 1, 1992·Pflügers Archiv : European journal of physiology·M C Sanguinetti, N K Jurkiewicz
Apr 1, 1991·Cardiovascular Drugs and Therapy·P F Cranefield, R S Aronson
Jul 1, 1986·Journal of the American College of Cardiology·D M RodenR L Woosley
Dec 1, 1987·Pflügers Archiv : European journal of physiology·H MatsuuraY Imoto
Jan 15, 1985·European Journal of Pharmacology·P R NemethJ D Wood
May 20, 1985·European Journal of Pharmacology·H J Cooke, H V Carey
Aug 24, 1995·Nature·P B BennettA L George
Apr 10, 1995·Archives of Internal Medicine·S BranJ P Palmer
Jul 1, 1994·Pflügers Archiv : European journal of physiology·P Daleau, J Turgeon
Jul 1, 1993·American Heart Journal·R MartynN Z Kerin
Feb 1, 1996·The Journal of Pediatrics·M B LewinR G Grifka
Jul 25, 1996·The New England Journal of Medicine·D K Wysowski, J Bacsanyi
May 1, 1996·The Journal of General Physiology·P S SpectorM C Sanguinetti

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Citations

Sep 22, 2000·Microscopy Research and Technique·G J BabuM Periasamy
Jun 25, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Ki-Wug Sung, Sang June Hahn
Feb 18, 2005·Cardiovascular Drugs and Therapy·Luigi CorvagliaGian Paolo Salvioli
Jun 6, 2007·Journal of Computer-aided Molecular Design·David J Diller, Doug W Hobbs
Nov 30, 2000·Current Treatment Options in Cardiovascular Medicine·S Viskin
Jun 30, 2001·European Journal of Pharmacology·B M DumotierM M Adamantidis
Oct 2, 2001·International Journal of Cardiology·S H WangS H Tsai
Apr 30, 1999·Molecular and Cellular Endocrinology·C K BauerJ R Schwarz
Jan 11, 2001·Journal of Pharmacological and Toxicological Methods·M R Gralinski
May 24, 2000·Progress in Pediatric Cardiology·C I Berul
Dec 14, 1999·Alimentary Pharmacology & Therapeutics·M ToniniF Crema
Sep 25, 2002·Alimentary Pharmacology & Therapeutics·G TougasM A Rojavin
Apr 12, 2001·The British Journal of Surgery·S Sunil, S Sinha
Mar 2, 2006·Toxicologic Pathology·Gary A GintantBryan F Cox
Nov 1, 2012·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Mathias WilhelmsGunnar Seemann
Feb 27, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·K YamamotoM Yamamoto
Aug 2, 2001·Journal of Pediatric Gastroenterology and Nutrition·A BenatarY Vandenplas
Oct 17, 2001·Journal of Cardiovascular Pharmacology·T YangD M Roden
May 31, 2003·Journal of Cardiovascular Pharmacology·Benoit DroletJacques Turgeon
Sep 10, 2003·Journal of Cardiovascular Pharmacology·Long-Mei WuMasayasu Hiraoka
Jan 13, 2004·Journal of Cardiovascular Pharmacology·Maria SzekeresAkos Koller
Jul 1, 2006·Current Opinion in Critical Care·Derek J RobertsRichard I Hall
Mar 12, 2011·Journal of Cardiovascular Pharmacology·Patrick VigneaultBenoit Drolet
Jan 19, 2013·Journal of Cardiovascular Pharmacology·Veronique Michaud, Jacques Turgeon
Feb 10, 2000·Pacing and Clinical Electrophysiology : PACE·K S NgB L Chia
Aug 5, 2000·Clinical Pharmacokinetics·E L Michalets, C R Williams
Jun 22, 2002·Pharmacology & Toxicology·Yoshihide Kii, Tsugutaka Ito
May 10, 2007·Canadian Journal of Physiology and Pharmacology·Pierre MorissetteJacques Turgeon
Dec 29, 2007·Journal of Pediatric Gastroenterology and Nutrition·Olivia LiemCarlo Di Lorenzo
Apr 25, 2007·Critical Reviews in Toxicology·Eran Bar-MeirUNKNOWN CBRN Medical Branch, Medical Corps, Israel Defense Forces

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