Pentisomide (CM 7857): A New Class I Antiarrhythmic Agent

Abstract

Pentisomide (CM7857, previously known as penticainide and propisomide), i.e., 2-(2-diisopropylaminoethyl)-4-methyl-2-(2-pyridyl)pentanamide, is a new antiarrhythmic agent derived from disopyramide ( Fig. 1). It is a white powder, soluble in water, and available in tablets of 150 and 200 mg for oral administration and in ampules of 200 mgi10 ml for intravenous administration. It is manufactured by Sanofi (France) and has been patented in France (approved June 26, 1982) since 1979. Preclinical and clinical studies have been conducted over the last 10 years (25). Electrophysiological studies have revealed that pentisomide possesses Vaughan-Williams class I (class I) antiarrhythmic actions (31). Clinical studies have shown that it is very well tolerated and effective in patients with ventricular (2,19-21,25,32) and supraventricular arrhythmias (1,17).This review aims to provide information on the pharmacology, toxicology, pharmacokinetics, and preliminary clinical experience with pentisomide. PHARMACOLOGYThe specific and general pharmacology of pentisomide has been extensively studied by researchers in Europe, North America, and Japan. Antiarchythmic Potential of PentisomideThe antiarrhythmic potential of pentisomide was studied in vivo in anesthetized and conscious canine models as well as in vitro in dog heart with ischemia-induced ventricular arrhythmias and in rat heart with reperfusion arrhythmias (26).In anesthetized dogs, pentisomide suppressed ouabain-induced ventricular tachycardia at intravenous doses of 1 to 5 mg/kg and was superior to the reference agents hydroquinidine and disopyramide. After intravenous administration, pentisomide at doses of 5 and