title: Comparison of the antiarrhythmic and the proarrhythmic effect of almokalant in anaesthetised rabbits.
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.
authors.affiliation: Department of Pharmacology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Farkas
authors.forename: I
authors.initials: I
authors.lastname: Leprán
authors.forename: J G
authors.initials: JG
authors.lastname: Papp
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D016171:Torsades de Pointes / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000316:Adrenergic alpha-Agonists; D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D010656:Phenylephrine; C074334:almokalant