Cardiotonic Activity of 5-Methyl-6-(4-pyridyl)-2H-1,4-thiazin-3 (4H)-one Hydrochloride (ZSY-27)
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概要
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Cardiotonic activity of a new, non-catecholamine and non-glycoside positive inotropic agent, 5-methyl-6-(4-pyridyl)-2H-1,4-thiazin-3 (4H)-one hydrochloride (ZSY-27), was investigated in isolated guinea pig left atria, cat right ventricular papillary muscle and cross-circulated excised dog papillary muscle preparations, and in anesthetized open-chest dogs. In electrically driven guinea pig left atria and cat papillary muscle preparations, ZSY-27 (3×10^<-6>-10^<-4>M) increased the developed tension in a concentration-related manner. The positive inotropic effect of ZSY-27 was not blocked by propranolol (3×10^<-8>M) in the guinea pig atria, but was significantly inhibited by carbachol (5×10^<-6>M) in cat papillary muscle preparations. The positive inotropic effect of ZSY-27 was comparable to that of milrinone in guinea pig atria. ZSY-27 (0.01-3mg) increased dose-dependently the developed tension in cross-circulated excised dog papillary muscle preparations as well. In anesthetized dogs, ZSY-27 (0.03-1 mg/kg, i.v.) produced a dose-dependent increase in left ventricular contractile force and a decrease in blood pressure, while the increase in heart rate was relatively small. The pharmacological profile of ZSY-27 in anesthetized dogs was similar to that of milrinone. These results suggest that ZSY-27 is potent cardiotonic agent with vasodilator activity and its effect may be partially due to an increase in the intracellular adenosine 3', 5'-cyclic monophosphate level.
- 公益社団法人日本薬学会の論文
著者
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YOSHIMURA Akira
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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YOSHIOKA Kimitomo
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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Hino Masataka
Research Laboratory Zenyaku Kogyo Co. Ltd.:hatano Research Institute Food And Drug Safety Center
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Ono H
Univ. Tokyo Tokyo Jpn
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YAMAZAKI Hiroaki
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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TAKASE Muneaki
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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ONO Hiroshi
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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Takase Muneaki
Research Laboratory Zenyaku Kogyo Co. Ltd.:hatano Research Institute Food And Drug Safety Center
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Yoshimura Akira
Research Laboratory Zenyaku Kogyo Co. Ltd.
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Yoshimura Akira
Research Laboratory Zenyaku Kogyo Co. Ltd.:hatano Research Institute Food And Drug Safety Center
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Yamazaki Hiroaki
Research Laboratory Zenyaku Kogyo Co. Ltd.
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Yamazaki Hiroaki
Research Laboratory Zenyaku Kogyo Co. Ltd.:hatano Research Institute Food And Drug Safety Center
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Yoshioka K
Research Laboratory Zenyaku Kogyo Co. Ltd.
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Yoshioka K
Zenyaku Kogyo Co. Ltd. Tokyo Jpn
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Yoshioka Kimitomo
Research Laboratory Zenyaku Kogyo Co. Ltd.
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