caa a22 4500 469079061 CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF00164584 doi (NATIONALLICENCE)springer-10.1007/BF00164584 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 [Elektronische Daten] [S. Nagashima, T. Uematsu, S. Araki, T. Matsuzaki, M. Fukuchi, H. Hashimoto, M. Nakashima] Summary: Antiarrhythmic and electrophysiological effects of SD-3212, a novel antiarrhythmic agent, which has both Na+ channel and Ca++ channel blocking activites, 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 (24h 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. SD-3212 increased the refractory period in the infarcted zone to a small extent (not significantly) at all strengths tested between 0.5-4 mA and also in the normal zone between 0.2-1 mA to an even lesser extent than in the infarcted zone. Bepridil produced a significant increase of refractory period in the infarcted zone. In the normal zone, bepridil produced a non-significant, but greater increase of the refractory period as compared with SD-3212. SD-3211 did not affect the refractory period in the infarcted zone or in the normal zone. None of the three drugs produced a significant change in the excitation threshold. Thus, SD-3212 showed electrophysiological properties of a drug with fast recovery kinetics without producing a significant increase of refractory period, and these properties are very similar to those of class Ib antiarrhythmic agents such as lidocaine. The present study suggests that there might be a possibility of SD-3212 to become a safe and unique antiarrhythmic agent with suppresses both Na+ and Ca++ inward current. Springer-Verlag, 1992 Na+ and Ca++ channel blocker nationallicence Ventricular arrhythmia nationallicence Intraventricular conduction nationallicence Refractory period nationallicence Myocardial infarction nationallicence Nagashima S. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut Uematsu T. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut Araki S. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut Matsuzaki T. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut Fukuchi M. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut Hashimoto H. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut Nakashima M. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 688-695 0028-1298 345:6<688 1992 345 210 https://doi.org/10.1007/BF00164584 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00164584 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nagashima S. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Uematsu T. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Araki S. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Matsuzaki T. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Fukuchi M. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Hashimoto H. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 700 1- Nakashima M. Department of Pharmacology, Hamamatsu University School of Medicine, 3600 Handa-Cho, 431-31, Hamamatsu, Japan aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 688-695 0028-1298 345:6<688 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer