Cardiovascular profile of a new anti-arrhythmic agent, SC-40230.
The cardiac and general haemodynamic effects of SC-40230, a newly developed anti-arrhythmic agent with both class 1a and 1b properties, were assessed in two different types of experiments using anaesthetised dogs, and in experiments using isolated cat papillary muscles. At the canine anti-arrhythmic dose (9 mg.kg-1 intravenously), SC-40230 decreased the maximum rate of rise of the left ventricular pressure (LV dP/dtmax) by 20%. It decreased heart rate slightly, and lowered (greater than 10%) blood pressure only at doses greater than the canine anti-arrhythmic dose. In these experiments there were dose dependent increases in the P-R interval and the QRS duration. In isolated cat papillary muscles, SC-40230 had a weak negative inotropic effect (IC20 = 3.3 X 10(-5) mol.litre-1) which was less than that previously reported for disopyramide phosphate (IC20 = 1.8 X 10(-5) mol.litre-1) or mexiletine (IC20 = 2.1 X 10(-5) mol.litre-1). These findings suggest SC-40230 has a minimal cardiovascular and haemodynamic side effect potential in its anti-arrhythmic dose range. If these results are confirmed in clinical studies, SC-40230 may have an improved side effect profile versus other anti-arrhythmic drugs such as disopyramide.
Frederick
L G
LG
Cardiovascular Diseases Research, Research and Development, GD Searle & Company, Skokie, Illinois 60077.
McDonald
S J
SJ
Garthwaite
S M
SM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002415:Cats; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C061991:bidisomide