Antiarrhythmic effects of an aconitine-like compound, TJN-505, on canine arrhythmia models.

Abstract

We examined the effects of an aconitine-like compound, TJN-505 (1alpha-16beta-dimethoxy-20-ethyl-14alpha-(4-methox ybenzoyloxy)-aconitan-8,13-diol hydrochloride), on canine arrhythmias provoked by digitalis, two-stage coronary ligation, adrenaline, programmed electrical stimulation, or aconitine. TJN-505 (2-2.5 mg/kg i.v.) suppressed digitalis-, two-stage coronary ligation- and adrenaline-induced ventricular arrhythmias. The antiarrhythmic plasma concentrations (IC50) of TJN-505 for these arrhythmia models were 1.26, 0.94 and 1.31 microg/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 effective refractory period and reduced the incidence of programmed electrical stimulation-induced arrhythmias in dogs with 7-day-old myocardial infarction (P < 0.05). TJN-505 (2 mg/kg i.v.) also suppressed the aconitine-induced atrial arrhythmias. In conclusion, TJN-505 suppressed various canine ventricular and atrial arrhythmias and seems to act as a blocker of multiple channels.

• Authors: J Arita, Y X Xue, N N Aye, K Fukuyama, Y Wakui, K Niitsu, M Maruno, C Siying, K Hashimoto
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 318 Issue 2-3 Pg. 333-40 (Dec 30 1996) ISSN: 0014-2999 [Print] Netherlands
• PMID: 9016923 (Publication Type: Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Calcium Channels
• Potassium Channels
• Sodium Channels
• TJN 505
• Aconitine
• Epinephrine

Topics

• Aconitine (analogs & derivatives, therapeutic use)
• Animals
• Anti-Arrhythmia Agents (therapeutic use)
• Arrhythmias, Cardiac (drug therapy)
• Calcium Channels (drug effects)
• Digitalis
• Dogs
• Electrocardiography
• Epinephrine
• Female
• Male
• Plants, Medicinal
• Plants, Toxic
• Potassium Channels (drug effects)
• Sodium Channels (drug effects)