Effects of the novel class Ia and class III antiarrhythmic agent RS-87337 on myocardial conduction in the anaesthetised dog.
The effects of the novel Class Ia/III antiarrhythmic compound RS-87337 on canine myocardial conduction were compared with those of the Class I antiarrhythmic disopyramide. RS-87337 had no effects on intra-atrial (I-A) or intra-ventricular (I-V) conduction parameters up to 10 mg.kg-1 i.v. (n = 6). Only one incidence of atrioventricular (A-V) block occurred at 10 mg.kg-1 at a pacing frequency of 261 beat.min-1. Disopyramide (5-10 mg.kg-1 i.v., n = 6) produced a frequency-dependent I-A conduction block and also significantly increased resting and paced A-V conduction times. Overall, disopyramide exhibited atrioselectivity while RS-87337 appeared more selective for ventricular conduction, possibly produced by a balance of its mixed Class Ia/III properties. RS-87337 was not cardiodepressant in the normal canine myocardium and produced no adverse effects on conduction parameters at doses up to 10 mg.kg-1 i.v.
Allely
M C
MC
Syntex Research Centre, Riccarton, Edinburgh, Scotland.
Alps
B J
BJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D004206:Disopyramide / Q000494:pharmacology; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D010879:Piperazines; C059276:RS 87337; D004206:Disopyramide