Cardiovascular effects of optical isomers of cibenzoline, assessed in the canine isolated, blood-perfused papillary muscle and sinoatrial node preparations.
A clinically available racemic mixture of the optical isomers of cibenzoline possesses a potent sodium channel-blocking action in addition to the moderate calcium channel-blocking action. It has been reported that the S(-)-isomer inhibits sodium channels more potently than calcium channels, whereas the R(+)-isomer suppresses the sodium channels as well as calcium channels, and that the calcium channel-blocking potency of these isomers is similar. This study was designed to assess the effects of each optical isomer of cibenzoline on ventricular contraction, coronary blood flow, and sinus node automaticity by using the canine isolated, blood-perfused papillary muscle and sinoatrial node preparations. Each isomer showed negative inotropic and chronotropic effects as well as coronary vasodilator action in a dose-dependent manner. The negative inotropic effect of S(-)-cibenzoline was 1.8 times more potent than that of R(+)-cibenzoline, whereas there was no significant difference between the isomers in the negative chronotropic and coronary vasodilator effects. These results suggest that the difference of the inotropic effects between the optical isomers of cibenzoline is mainly derived from the extent of the sodium channel-blocking action, whereas the vasodilator and negative chronotropic effects may chiefly depend on the calcium channel inhibition.
Takehana
S
S
Department of Pharmacology, Yamanashi Medical University, Nakakoma-gun, Japan.
Sugiyama
A
A
Hashimoto
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D010477:Perfusion; D012849:Sinoatrial Node / Q000187:drug effects*; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; C032151:cifenline