Antiarrhythmic and electrophysiological effects of SD-3212, a novel Na+ and Ca++ channel blocker, in anaesthetized dogs with myocardial infarction in comparison with its stereoisomer (SD-3211) and bepridil.
Antiarrhythmic and electrophysiological effects of SD-3212, a novel antiarrhythmic agent, which has both Na+ channel and Ca++ channel blocking activities, were compared with those of its (+)-stereoisomer, SD-3211, which has only a Ca++ channel blocking activity, and bepridil, a known Ca++ channel blocker with additional Na+ channel blocking activity, using the two-stage coronary ligation induced arrhythmia (24 h after the ligation of the left anterior descending coronary artery) and 7 day-old myocardial infarcted hearts in anaesthetized dogs. SD-3212 showed a dose-dependent antiarrhythmic effect on the two-stage coronary ligation induced arrhythmia. SD-3212 at a dose of 3 mg/kg reduced the arrhythmic ratio, i.e. ectopic beats per min divided by the sum of ectopic beats and sinus beats per min, significantly from 1 up to 12 min after the administration. Neither bepridil (1-6 mg/kg) nor SD-3211 (1 mg/kg) had an antiarrhythmic effect. SD-3212 (0.3-3 mg/kg) prolonged both the conduction time in the normal myocardium and the delayed potential in the infarcted myocardium in the 7 day-old myocardial infarcted hearts in anaesthetized dogs in a dose-dependent manner. This effect of SD-3212 was shown at coupling intervals of 150-1000 ms increasing with decreasing interval. In this respect, SD-3212 is similar to drugs which show fast recovery of Vmax from use-dependent block such as lidocaine. Bepidril (1-6 mg/kg) also prolonged these parameters in a dose-dependent manner, however, the prolongation induced by bedripil was limited to shorter coupling intervals as compared with that induced by SD-3212. SD-3212 (0.1-1 mg/kg) did not show this prolonging effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Nagashima
S
S
Department of Pharmacology, Hamamatus University School of Medicine, Japan.
Uematsu
T
T
Araki
S
S
Matsuzaki
T
T
Fukuchi
M
M
Hashimoto
H
H
Nakashima
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015764:Bepridil / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D015222:Sodium Channels / Q000187:drug effects*; D013237:Stereoisomerism; D013844:Thiazoles / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D015222:Sodium Channels; D013844:Thiazoles; D015764:Bepridil; C064356:sesamodil