Effects of a new class I antiarrhythmic drug bidisomide on canine ventricular arrhythmia models.
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.
Zhenjiu
W
W
Department of Pharmacology, Yamanashi Medical College, Japan.
Awaji
T
T
Hirasawa
A
A
Motomura
S
S
Hashimoto
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D004071:Digitalis Glycosides / Q000037:antagonists & inhibitors; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004837:Epinephrine / Q000037:antagonists & inhibitors; D005260:Female; D009200:Myocardial Contraction / Q000187:drug effects*; D010880:Piperidines / Q000097:blood / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D004071:Digitalis Glycosides; D010880:Piperidines; C061991:bidisomide; D004837:Epinephrine