Effects of a new antiarrhythmic drug TYB-3823 on canine ventricular arrhythmia models.
The antiarrhythmic and direct cardiovascular effects of a new antiarrhythmic agent, TYB-3823 [1-(2,6-dimethylphenyl)-4,4-dimethyl-aminoguanidine hydrochloride], were investigated. To determine the antiarrhythmic effects, spontaneously occurring adrenaline-, digitalis-, and two-stage coronary ligation-induced arrhythmias were used. TYB-3823 suppressed these three arrhythmia models. The antiarrhythmic plasma concentrations, IC50, of TYB-3823 for digitalis-, coronary ligation-, and adrenaline-induced arrhythmias were 7.8, 16.8, and 5.0 micrograms/ml, respectively. In the blood perfused sinoatrial (SA) node and papillary muscle (PM) preparations, TYB-3823 decreased the sinoatrial rate (SAR) and contractile force following an initial small positive inotropic effect and increased the intraventricular conduction time and coronary blood flow. These results indicate that TYB-3823 is similar to other class I antiarrhythmic agents, such as aprindine and nicainoprol, in the antiarrhythmic profile and is expected to become a clinically useful antiarrhythmic drug.
Hashimoto
K
K
Department of Pharmacology, Yamanashi Medical College, Japan.
Sugiyama
A
A
Haruno
A
A
Matsuzaki
T
T
Hirasawa
A
A
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine; D005260:Female; D006146:Guanidines / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D010042:Ouabain; D016276:Ventricular Function / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; C059816:restacorin; D010042:Ouabain; D004837:Epinephrine