Comparison of the antiarrhythmic and the proarrhythmic effect of almokalant in anaesthetised rabbits

European Journal of Pharmacology
A S FarkasJ G Papp

Abstract

In this study the antiarrhythmic and the proarrhythmic activities of almokalant, a selective class III antiarrhythmic agent, were compared. The antiarrhythmic effect of the drug was tested in pentobarbital-anaesthetised rabbits. Arrhythmia was evoked by occluding and releasing the left circumflex coronary artery. Almokalant in a dose of 250 nmol/kg i.v., significantly decreased the incidence of reperfusion induced ventricular fibrillation (21% vs. 75% in the control group) and increased the proportion of surviving animals during reperfusion (86% vs. 42%). The proarrhythmic effect of almokalant was examined during alpha1-adrenoceptor stimulation in chloralose-anaesthetised rabbits. Almokalant (75 nmol/kg per min) triggered torsade de pointes arrhythmias in 8 animals out of 11. The dose of almokalant (mean+/-S.E.M.) required to produce this effect was 1181+/-519 nmol/kg. It is concluded that, although almokalant is an effective antiarrhythmic agent against ischaemia-reperfusion induced arrhythmias, it has marked proarrhythmic activity during alpha1-adrenoceptor stimulation.

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Citations

Aug 7, 2002·European Journal of Pharmacology·András Farkas, Susan J Coker
Aug 23, 2002·Pharmacology & Therapeutics·Alan Wickenden
Jun 14, 2013·Journal of Pharmacology & Pharmacotherapeutics·Shailaja B KhobragadeVyas M Shingatgeri
Aug 27, 2014·Journal of Cardiovascular Electrophysiology·Rosanne VarkevisserMarcel A VAN DER Heyden
Nov 3, 2004·Journal of Pharmacological and Toxicological Methods·András FarkasSusan J Coker
Jun 19, 2008·Pharmacology & Therapeutics·Leif Carlsson

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