Inhibitory Effect of KW-3049,A New 1,4-Dihydropyridine Calcium Antagonist, on the Reduction of Myocardial Creatine Kinase Activity and High-Energy Phosphate Content in Rats Subjected to Coronary Artery Ligation
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概要
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The effect of KW-3049,(±)-(R^*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid (R^*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride on myocardial infarction in rats was examined, in comparison with some other drugs. Extension of myocardial infarction was assessed by separately determining the tissue creatine kinase (CK) activity of left ventricular free wall (LVFW) and that of interventricular septum. Loss of CK activity was limited to LVFW until 6 h after the ligation of the left main coronary artery, while 24 h after the ligation, it extended to the septum. Therefore, the effects of drugs were examined mainly in rats following 6 h of coronary artery ligation. Pretreatments with KW-3049 at 1 and 3 mg/kg (p.o.), given 1 h before coronary artery ligation, significantly reduced the loss of CK activity of LVFW by 45.3 and 39.7%, respectively. Also, posttreatment with KW-3049 at 30 μg/kg (i.p.), given 10 min after the ligation, significantly reduced the loss of CK activity by 30.6%. On the other hand, nifedipine (3,10 mg/kg, p.o.), propranolol (100 mg/kg, p.o.), OKY-1581 (100 mg/kg, p.o.) and BM 13.177 (100 mg/kg, p.o.), each of which was given 1 h before coronary ligation, did not significantly reduced the loss of CK activity. Coronary artery ligation for 6 h significantly decreased the myocardial contents of adenosine triphosphate (ATP) and creatine phosphate (CP). Pretreatments with KW-3049 at 1 and 3 mg/kg (p.o.) reduced the decrease in ATP and CP. These results suggest that KW-3049 possesses a superior cardioprotective effect in comparison with the other drugs examined. The possible implications for the protection by KW-3049 are discussed.
- 公益社団法人日本薬学会の論文
著者
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Karasawa Akira
Pharmaceuticals Research Laboratory Kyowa Hakko Kogyo Co. Ltd.
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Kubo K
Department Of Pharmacology Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Kubo Kazuhiro
Pharmaceutical Research Laboratories Of Kyowa Hakko Kogyo Co. Ltd.
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Kubo Kazuhiro
Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Kubo Kazuhiro
Department Of Pharmacology Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Karasawa Akira
Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Karasawa Akira
Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.
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