ANTIARRHYTHMIC EFFECTS OF AN ACONITINE-LIKE COMPOUND, TJN-505, ON CANINE ARRHYTHMIA MODELS

We examined the effects of an aconitine-like compound, TJN-505 (1 alph a-16 beta-dimethoxy-20-ethyl-14 alpha-(4-methoxybenzoyloxy)-aconitan-8 ,13-diol hydrochloride), on canine arrhythmias provoked by digitalis, two-stage coronary ligation, adrenaline, programmed electrical stimula tion, or aconitine. TJN-505 (2-2.5 mg/kg i.v.) suppressed digitalis-, two-stage coronary ligation- and adrenaline-induced ventricular arrhyt hmias. The antiarrhythmic plasma concentrations (IC50) of TJN-505 for these arrhythmia models were 1.26, 0.94 and 1.31 mu g/ml, respectively . TJN-505 (2 mg/kg i.v. followed by the infusion of 0.1 mg/kg per min) prolonged PR, QRS, QTc and JTc intervals and the ventricular effectiv e refractory period and reduced the incidence of programmed electrical stimulation-induced arrhythmias in dogs with 7-day-old myocardial inf arction (P < 0.05). TJN-505 (2 mg/kg i.v.) also suppressed the aconiti ne-induced atrial arrhythmias. In conclusion, TJN-505 suppressed vario us canine ventricular and atrial arrhythmias and seems to act as a blo cker of multiple channels.