Antiarrhythmic effect of a new class 1 antiarrhythmic drug, AN-132, on ventricular arrhythmias in beagles.
Using two-stage coronary-ligation-, digitalis- and adrenaline-induced ventricular arrhythmias in beagles, antiarrhythmic effects of AN-132 were examined, and the minimum effective plasma concentration for each arrhythmia model was determined. AN-132 suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-hour coronary ligation, 48-hour coronary ligation, digitalis, and adrenaline were 3.4-4.6, 1.5-2.3, 0.83, and 9.3 micrograms/ml, respectively. The concentration for adrenaline-induced arrhythmia was significantly higher than that of 24-hour coronary ligation arrhythmia, and it was also higher than that of digitalis arrhythmia. This pharmacologic profile is similar to those of pirmenol and mexiletine. Since AN-132 had no deleterious effects on the hemodynamics and the central nervous system, it may become a clinically useful antiarrhythmic drug.
Hashimoto
K
K
Department of Pharmacology, Yamanashi Medical College, Tamaho-cho, Japan.
Watanabe
K
K
Mitsuhashi
H
H
D000813:Anilides / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D003331:Coronary Vessels / Q000502:physiology / Q000601:surgery; D004070:Digitalis; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000633:toxicity; D005029:Ethylenediamines / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008026:Ligation; D008297:Male; D010946:Plants, Medicinal; D010947:Plants, Toxic; D013610:Tachycardia / Q000188:drug therapy*; D016276:Ventricular Function / Q000187:drug effects*
C053205:3-(diisopropylaminoethylamino)-2',6'-dimethylpropionanilide, diphosphoric acid; D000813:Anilides; D000889:Anti-Arrhythmia Agents; D005029:Ethylenediamines; D004837:Epinephrine