Antiarrhythmic effects of a new drug, E-0747, on canine ventricular arrhythmia models.
Antiarrhythmic effects of a new antiarrhythmic drug, E-0747, were examined using four canine ventricular arrhythmia models: digitalis-, adrenaline- and two-stage coronary ligation-induced arrhythmias and a newly developed locally-induced digitalis arrhythmia. The minimum effective plasma concentration of E-0747 was determined for the first three arrhythmia models. E-0747 suppressed those arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by digitalis, adrenaline, 24 hr coronary ligation, and 48 hr coronary ligation were 1.4 +/- 0.6, 1.8 +/- 0.4, 1.6 +/- 0.4 and 2.2 +/- 0.2 micrograms/ml, respectively (mean +/- S.D., n = 5-10). The aforementioned minimum effective plasma concentrations of E-0747 for these arrhythmias were almost equal to the reported concentration in vitro to suppress the Na channels of isolated canine ventricular tissues. The class 1 property of E-0747 was also shown in a newly developed locally-induced digitalis arrhythmia. Thus E-0747 suppresses arrhythmia by inhibiting Na channels of cardiac cells and is expected to become a clinically useful antiarrhythmic drug.
Mitsuhashi
H
H
Department of Pharmacology, Yamanashi Medical College, Japan.
Akiyama
K
K
Hashimoto
K
K
Sawa
Y
Y
Hatori
Y
Y
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000601:surgery; D004285:Dogs; D004837:Epinephrine; D005260:Female; D008026:Ligation; D008297:Male; D010042:Ouabain; D010880:Piperidines / Q000097:blood / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D010042:Ouabain; C051825:E 0747; D004837:Epinephrine