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Effect of SC‐40230, a new class I antiarrhythmic agent, on canine ventricular tachycardias
Author(s) -
Garthwaite S.,
Hatley Frida,
Frederick Leo,
Ruby Jeanette,
Cook Chyung
Publication year - 1989
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430170204
Subject(s) - ouabain , medicine , ligation , cardiology , sinus rhythm , antiarrhythmic agent , fissipedia , anesthesia , ventricular tachycardia , pharmacology , chemistry , atrial fibrillation , heart disease , sodium , organic chemistry
SC‐40230, α‐[2‐[acetyl(1‐methylethyl)amino]ethyl]‐α‐(2‐chlorophenyl)‐1‐piperidinebutanamide, a new class I antiarrhythmic agent, was tested for efficacy against coronary ligation‐induced arrhythmias and ouabain toxicity arrhythmias in dogs. Doses of 9mg/kg i.v. and 15, 25, and 35 mg/kg p.o. significantly reduced ectopic rate in conscious dogs that had undergone ligation of the left anterior descending coronary artery 24 hr prior to testing. Plasma concentrations of SC‐40230 ranging from 3 to 9 μg/ml corresponded with ectopic rate reductions of 10–82% in the coronary ligation model. SC‐40230 was well tolerated at all doses tested in the conscious dogs. A 5 mg/kg i.v. dose of SC‐40230 converted ouabain‐induced ventricular tachycardias to normal sinus rhythm in anesthetized dogs. The antiarrhythmic effect of SC‐40230 in the ouabain toxicity model was reversed by large (⪇ 240 U) doses of insulin. The experiments described in this study demonstrated that SC‐40230 is a well‐tolerated new class I antiarrhythmic agent with intravenous and oral effectiveness against ventricular arrhythmias.