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.
Central Research Laboratories, Santen Pharmaceutical Company Limited, Osaka, Japan.
N
N
Miyawaki
T
T
Furuta
T
T
Shigei
F
F
Yamazaki
H
H
Yamauchi
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