1-[4-(2-ter-butyl-quinolyl)]-3-(4-piperidyl)propanol (PK 10139): a new potent and long-acting antiarrhythmic agent

M Mestre, G Bouetard, G Le Fur, C Renault, C Gueremy and A Uzan

PK 10139 is a new synthetic quinoline antiarrhythmic agent 10 times more potent and at least 2 to 3 times longer acting than quinidine sulfate. In the dog, the near 100% active dose (1.5 mg/kg i.v.) completely converted to sinus rhythm ouabain-induced ventricular tachycardia for over 30 min. The efficacy of this compound against multifocal beats induced by two-stage ligation of the left coronary artery (Harris) in the conscious dog was demonstrated after i.v. and oral administration with no peripheral and central nervous system side effects after the higher effective dose contrary to quinidine. In the anesthetized dog, PK 10139 like quinidine, increased atrial, atrioventricular nodal and ventricular refractory periods as determined with the programmed extrastimulus technique. PK 10139 also increased electrical stimulus threshold and intracardiac conduction times evaluated by measurement of A-H nodal conduction time, H-V conduction time and QRS interval as seen with all the class I antiarrhythmic agents. Thus, PK 10139 is a much more potent and long-acting agent than quinidine, with better tolerance.

Volume 225, Issue 1, pp. 158-163, 04/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics