Cardiac electrophysiological effects of MS-551, a novel class III antiarrhythmic agent

• Published in: Japanese Journal of Pharmacology Vol. 52; no. suppl-1.1; p. 250
• Main Authors: Ishii, Masaaki, Katakami, Tsutomu, Yokoyama, Tatsuro, Banno, Hitoshi, Hirayama, Makoto, Kamiya, Joji
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1990
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)55574-3

MS-551(MS) is a newly synthesized class III antiarrhythmic agent devoid of benzensulfonamide moiety. The cardiac electrophysiological effects of MS were studied in isolated cardiac tissues and anesthetized dogs. In microelectrode studies on canine Purkinje fibers, MS (0.1-10 ug/ml) produced a concentration dependent increase (8-69%) in action potential duration without a change in resting membrane potential, AP amplitude and Vmax. In anesthetized dogs, MS (0.03-10 mg/kg i.v.) dose-dependently increased effective refractory periods in atrium(AERP) and ventricle(VERP).Increase in VERP was correlated to QT interval prolongation. At 1 mg/kg, AERP and VERP were increased 42% and 20%, respectively. MS caused a slight decrease in heart rate with QT(c) prolongation in a dose-dependent manner, but MS up to 10 mg/kg i.v. did not produce a significant change in PQ and QRS intervals, mean blood pressure, aortic flow, myocardial contractility and intracardiac conduction time (A-H, H-V). Thus, MS appears to be a selective class III antiarrhythmic agent with a favourable hemodynamic profile.