Antiarrhythmic profile of a new class 1 drug, AHR 10718, on canine atrial and ventricular arrhythmia models.
Antiarrhythmic effects of AHR 10718 were examined using two-stage coronary ligation, digitalis and adrenaline-induced canine ventricular arrhythmias and aconitine-induced canine atrial arrhythmia. The minimum effective plasma concentration for each arrhythmia model was determined for quantitative analysis of the antiarrhythmic effects. AHR 10718 suppressed the above arrhythmias except for adrenaline-induced arrhythmia. The minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation, 48 hr coronary ligation and digitalis were 8.1 +/- 0.7 (by 10 mg/kg, i.v.), 2.9 +/- 0.9 (by 5 mg/kg, i.v.) and 2.8 +/- 0.6 (by 5 mg/kg, i.v.) microgram/ml, respectively (mean +/- S.D., n = 6). The correlation coefficients between the antiarrhythmic effects of AHR 10718 and its plasma concentrations were not high. This pharmacological profile is characteristic of class 1 Na channel blockers, and in particular, it is similar to those of disopyramide, procainamide and SUN 1165 from our previous studies. AHR 10718 is expected to become a clinically useful antiarrhythmic drug.
Mitsuhashi
H
H
Department of Pharmacology, Yamanashi Medical College, Japan.
Hashimoto
K
K
D000157:Aconitine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004071:Digitalis Glycosides; D004285:Dogs; D004837:Epinephrine; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D010671:Phenylurea Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D004071:Digitalis Glycosides; D010671:Phenylurea Compounds; C045188:AHR 10718; D000157:Aconitine; D004837:Epinephrine