The antiarrhythmic and direct cardiovascular effects of a new antiarrhythmic agent,
bidisomide, alpha-(2-[acetyl(1-methylethyl)amino]ethyl)-alpha-(2- chlorophenyl)-1-piperidinebutanamide, were investigated. To determine the
anti-arrhythmic effects, spontaneously occurring
adrenaline-, digitalis- and two-stage coronary
ligation-induced arrhythmias were used.
Bidisomide suppressed these three
arrhythmia models. The antiarrhythmic plasma concentration, IC50, of
bidisomide for digitalis-induced
arrhythmia was 22.1 micrograms/ml, and those calculated for intravenous
bidisomide in 24 h and 48 h coronary
ligation-arrhythmias were 15.1 and 11.6 micrograms/ml and that calculated for oral
bidisomide in 24 h coronary
ligation-
arrhythmia was 5.4 micrograms/ml and that for
adrenaline induced
arrhythmia was 58.7 micrograms/ml. In the blood perfused sinoatrial node and papillary muscle preparations,
bidisomide decreased the sinoatrial rate and contractile force and increased the intraventricular conduction time and coronary blood flow. These results indicate that
bidisomide is similar to other class I antiarrhythmic agents such as
pirmenol and KW-3401 in its antiarrhythmic profile and is expected to become a clinically useful
antiarrhythmic drug.