Anti-ischaemic and vasospasmolytic effects of a novel Ca2+ channel blocker, SD-3211, in vitro.

Abstract

1. The present study was undertaken to determine the vasospasmolytic activity of a novel non-dihydropyridine type of Ca2+ channel blocker, SD-3211, in isolated canine coronary arteries and its ability to reduce myocardial ischaemic damage in isolated perfused rabbit hearts. 2. The vasospasmolytic effect of SD-3211 was investigated using 3,4-diaminopyridine-induced rhythmic contraction, in comparison with its enantiomer (SD-3212), nicardipine and diltiazem. SD-3211 was shown to reduce the peak tension and increase the contraction frequency. The order of potency for the relaxation of the peak tension was as follows: nicardipine greater than SD-3211 greater than diltiazem greater than SD-3212 and being compatible with that for the relaxant effects of these compounds on KCl-induced contraction in the same specimen. 3. Furthermore, the effect of SD-3211 on myocardial damage due to global ischaemia for 60 min followed by 60 min of reperfusion was examined. SD-3211 at a concentration of 2 X 10(-8) mol/L was given for 40 min before and again for 60 min after the ischaemia. SD-3211 attenuated the increase in leakage of creatine phosphokinase from the hearts and the decrease in pH of perfusate during reperfusion, while concomitantly providing a significant improvement in the post-ischaemic recovery of developed tension. 4. These results suggest that SD-3211 has properties to reduce coronary vasospasm and to provide protection against ischaemic damage, both of which may have beneficial actions in the treatment of ischaemic heart disease.

• Authors: N Miyawaki, T Furuta, T Shigei, F Yamazaki, H Yamauchi
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 18 Issue 8 Pg. 579-85 (Aug 1991) ISSN: 0305-1870 [Print] Australia
• PMID: 1914255 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Potassium Channels
• Thiazoles
• 4-Aminopyridine
• sesamodil
• Amifampridine

Topics

• 4-Aminopyridine (analogs & derivatives, pharmacology)
• Amifampridine
• Animals
• Arteries (drug effects)
• Calcium Channel Blockers (pharmacology)
• Coronary Disease (drug therapy)
• Coronary Vasospasm (drug therapy)
• Coronary Vessels (drug effects)
• Dogs
• In Vitro Techniques
• Myocardial Reperfusion
• Potassium Channels (drug effects)
• Rabbits
• Thiazoles (pharmacology, therapeutic use)
• Vasoconstriction