Anti-ischaemic and vasospasmolytic effects of a novel Ca2+ channel blocker, SD-3211, in vitro.
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.
Miyawaki
N
N
Central Research Laboratories, Santen Pharmaceutical Company Limited, Osaka, Japan.
Furuta
T
T
Shigei
T
T
Yamazaki
F
F
Yamauchi
H
H
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000188:drug therapy*; D003329:Coronary Vasospasm / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D066298:In Vitro Techniques; D015425:Myocardial Reperfusion; D015221:Potassium Channels / Q000187:drug effects; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014661:Vasoconstriction
D002121:Calcium Channel Blockers; D015221:Potassium Channels; D013844:Thiazoles; D015761:4-Aminopyridine; C064356:sesamodil; D000077770:Amifampridine