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Published on: October 18, 2018

SCH00013, a novel Ca(2+) sensitizer with positive inotropic and no chronotropic action in heart failure

Naoto Tadano1, Sachio Morimoto, Akira Yoshimura

  • 1Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Journal of Pharmacological Sciences
|January 13, 2005
PubMed

Insights

SCH00013 is a novel calcium sensitizer that enhances cardiac muscle force generation. It shows a positive inotropic effect in heart failure without affecting heart rate, likely by improving the Frank-Starling mechanism.

Area of Science:

  • Cardiovascular Pharmacology
  • Cardiac Physiology

Background:

  • Heart failure is a complex condition characterized by impaired cardiac contractility.
  • Calcium sensitizers offer a therapeutic approach to enhance myocardial function.

Purpose of the Study:

  • To investigate the effects of SCH00013 on calcium-induced force generation in cardiac muscle.
  • To evaluate the in vivo cardiac function of SCH00013 in a canine model of heart failure.

Main Methods:

  • Skinned cardiac muscle fiber preparations from rabbits were used to assess Ca(2+)-induced force generation.
  • In vivo studies in dogs with high-pacing-induced heart failure evaluated cardiac function after intravenous administration of SCH00013.

Main Results:

  • SCH00013 demonstrated a significant calcium sensitizing effect in skinned cardiac muscle fibers at physiological pH (7.2-7.4) and longer sarcomere lengths.
  • In vivo, SCH00013 elicited a dose-dependent positive inotropic effect in normal and heart failure dogs, with no observed chronotropic action.
  • No significant difference in calcium sensitizing action was found between SCH00013 enantiomers.

Conclusions:

  • SCH00013 is a novel calcium sensitizer with positive inotropic properties and no chronotropic effects in heart failure.
  • The findings suggest SCH00013 may enhance cardiac function by augmenting the Frank-Starling mechanism.

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