Electrophysiologic, antiarrhythmic and hemodynamic effects of transcainide.
Transcainide was selected as an antiarrhythmic drug with potential clinical application. In isolated dog, sheep and rabbit Purkinje fibres, in dog and guinea-pig trabecular preparations and in the guinea-pig right auricle, transcainide decreases the rate of rise of the transmembrane action potential, with no effect on normal spontaneous activity and calcium-mediated action potentials; it inhibits early after-depolarizations. The effect on the rate of rise is very slow in onset. In vivo a prolongation of QRS duration is observed. In dogs, the drug is effective against post-infarction and ouabain-induced ventricular arrhythmias, and abolishes acetylcholine and aconitine-induced atrial fibrillation; it elevates the threshold of electrically induced ventricular fibrillation. Hemodynamic studies in anaesthetized and unaesthetized dogs indicate that transcainide moderately decreases contractility, while slightly increasing frequency. No major side effects are seen. Preliminary data on the pharmacokinetics suggest that in the dog the observed effects after i.v. infusion are related to the parent drug. Transcainide is an antiarrhythmic of the local anaesthetic type, with very slow kinetics. It is characterized by a good oral absorption and a long duration of action.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000633:toxicity; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000503:physiopathology; D002118:Calcium / Q000502:physiology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D011690:Purkinje Fibers / Q000187:drug effects; D011817:Rabbits; D012756:Sheep; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; C052070:transcainide; D008012:Lidocaine; D002118:Calcium