SCH00013, a Novel Ca2+ Sensitizer With Positive Inotropic and No Chronotropic Action in Heart Failure
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概要
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We investigated the effects of the agent SCH00013 on Ca2+-induced force generation in rabbit skinned cardiac muscle fibers and in vivo cardiac function in high-pacing-induced heart failure dogs. The Ca2+-induced force generation in skinned cardiac muscle fibers was determined at pH 6.2 – 7.4, and SCH00013 was found to have a significant Ca2+ sensitizing effect at pH 7.2 to 7.4. There was no significant difference in the Ca2+ sensitizing action between the enantiomers of SCH00013. The Ca2+ sensitizing effect of SCH00013 was dependent on the sarcomere length, being significant only at a long sarcomere length. SCH00013 elicited a positive inotropic effect at more than 0.3 and 1 mg/kg, i.v. in normal and heart failure dogs, respectively, with no chronotropic action. These results strongly suggested that SCH00013 is a novel Ca2+ sensitizer that elicits a positive inotropic and no chronotropic effect in heart failure, probably through enhancing the Frank-Starling mechanism.
- 社団法人 日本薬理学会の論文
著者
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Miwa Yoshikazu
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University
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Sasaguri Toshiyuki
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University
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Morimoto S
Dep. Of Clinical Pharmacology Fac. Of Medical Sciences Kyushu Univ. Jpn
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Morimoto Sachio
Department Of Clinical Pharmacology Faculty Of Medical Science Kyushu University
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Miwa Yoshikazu
Department Of Clinical Pharmacology Faculty Of Medical Sciences Kyushu University
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OHTSUKI Iwao
Department of Pharmacology, Faculty of Medicine, Kyushu University
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TADANO Naoto
Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University
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YOSHIMURA Akira
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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MIURA Makoto
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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YOSHIOKA Kimitomo
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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SAKATO Mitsuo
Research Laboratory, Zenyaku Kogyo Co., Ltd.
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Takahashi-Yanaga Fumi
Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University
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Ohtsuki Iwao
Department Of Clinical Pharmacology Faculty Of Medicine Kyushu University
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Tadano Naoto
Department Of Clinical Pharmacology Graduate School Of Medical Sciences Kyushu University
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Sakato Mitsuo
Research Laboratory Zenyaku Kogyo Co. Ltd.
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Yoshimura Akira
Research Laboratory Zenyaku Kogyo Co. Ltd.
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Morimoto S
Faculty Of Medical Sciences Department Of Clinical Pharmacology Kyushu University
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Yoshioka Kimitomo
Research Laboratory Zenyaku Kogyo Co. Ltd.
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Sasaguri Toshiyuki
Department Of Clinical Pharmacology Faculty Of Medical Sciences Kyushu University
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Miura Makoto
Research Laboratory Zenyaku Kogyo Co. Ltd.
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