Antiarrhythmic effects of an aconitine-like compound, TJN-505, on canine arrhythmia models.
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.
Arita
J
J
Department of Pharmacology, Yamanashi Medical University, Tamaho-cho, Nakakoma-gun, Japan.
Xue
Y X
YX
Aye
N N
NN
Fukuyama
K
K
Wakui
Y
Y
Niitsu
K
K
Maruno
M
M
Siying
C
C
Hashimoto
K
K
D000157:Aconitine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D015220:Calcium Channels / Q000187:drug effects; D004070:Digitalis; D004285:Dogs; D004562:Electrocardiography; D004837:Epinephrine; D005260:Female; D008297:Male; D010946:Plants, Medicinal; D010947:Plants, Toxic; D015221:Potassium Channels / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D015221:Potassium Channels; D015222:Sodium Channels; C105772:TJN 505; D000157:Aconitine; D004837:Epinephrine