SCH00013, a novel Ca2+ sensitizer with positive inotropic and no chronotropic action in heart failure

Naoto Tadano, Sachio Morimoto, Akira Yoshimura, Makoto Miura, Kimitomo Yoshioka, Mitsuo Sakato, Iwao Ohtsuki, Yoshikazu Miwa, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 Ca 2+-induced force generation in skinned cardiac muscle fibers was determined at pH 6.2-7.4, and SCH00013 was found to have a significant Ca 2+ 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.

Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalJournal of Pharmacological Sciences
Volume97
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

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Heart Failure
Sarcomeres
Myocardium
Dogs
Starlings
Sch 00013
Rabbits

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

SCH00013, a novel Ca2+ sensitizer with positive inotropic and no chronotropic action in heart failure. / Tadano, Naoto; Morimoto, Sachio; Yoshimura, Akira; Miura, Makoto; Yoshioka, Kimitomo; Sakato, Mitsuo; Ohtsuki, Iwao; Miwa, Yoshikazu; Takahashi-Yanaga, Fumi; Sasaguri, Toshiyuki.

In: Journal of Pharmacological Sciences, Vol. 97, No. 1, 01.01.2005, p. 53-60.

Research output: Contribution to journalArticle

Tadano, N, Morimoto, S, Yoshimura, A, Miura, M, Yoshioka, K, Sakato, M, Ohtsuki, I, Miwa, Y, Takahashi-Yanaga, F & Sasaguri, T 2005, 'SCH00013, a novel Ca2+ sensitizer with positive inotropic and no chronotropic action in heart failure', Journal of Pharmacological Sciences, vol. 97, no. 1, pp. 53-60. https://doi.org/10.1254/jphs.FP0040654
Tadano, Naoto ; Morimoto, Sachio ; Yoshimura, Akira ; Miura, Makoto ; Yoshioka, Kimitomo ; Sakato, Mitsuo ; Ohtsuki, Iwao ; Miwa, Yoshikazu ; Takahashi-Yanaga, Fumi ; Sasaguri, Toshiyuki. / SCH00013, a novel Ca2+ sensitizer with positive inotropic and no chronotropic action in heart failure. In: Journal of Pharmacological Sciences. 2005 ; Vol. 97, No. 1. pp. 53-60.
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