Efficacy and plasma concentrations of SC-36602 in canine models of ventricular arrhythmia.
The antiarrhythmic effectiveness of a new class I agent, SC-36602, was evaluated in two canine models of ventricular arrhythmia. In a Harris coronary ligation-induced arrhythmia model, SC-36602 significantly reduced ectopic rate at doses of 8 mg/kg i.v. and 15, 20 and 30 mg/kg per os. In a ouabain-induced arrhythmia model, a 9 mg/kg i.v. dose of SC-36602 had a sustained (greater than or equal to 60 min) antiarrhythmic effect. The approximate plasma concentration of SC-36602 necessary for measurable antiarrhythmic activity was estimated to be 2-7 micrograms/ml after either i.v. or oral administration. No adverse cardiovascular or central nervous system effects were observed in conscious or anesthetized dogs in response to SC-36602.
Garthwaite
S M
SM
Department of Cardiovascular Diseases Research, Searle Research and Development, Skokie, Illinois 60077.
Hatley
F R
FR
Frederick
L G
LG
Cook
C
C
D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D010042:Ouabain; D011188:Potassium / Q000097:blood; D011744:Pyrimidinones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D001786:Blood Glucose; D011744:Pyrimidinones; D010042:Ouabain; C051827:SC 36602; D011188:Potassium