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

Abstract

We investigated the effects of the agent SCH00013 on Ca(2+)-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 Ca(2+) sensitizing action between the enantiomers of SCH00013. The Ca(2+) 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 Ca(2+) sensitizer that elicits a positive inotropic and no chronotropic effect in heart failure, probably through enhancing the Frank-Starling mechanism.

• Authors: Naoto Tadano, Sachio Morimoto, Akira Yoshimura, Makoto Miura, Kimitomo Yoshioka, Mitsuo Sakato, Iwao Ohtsuki, Yoshikazu Miwa, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 97 Issue 1 Pg. 53-60 (Jan 2005) ISSN: 1347-8613 [Print] Japan
• PMID: 15644593 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cardiotonic Agents
• Dihydropyridines
• Pyridazines
• Sch 00013
• Amrinone
• Calcium

Topics

• Amrinone (pharmacology)
• Animals
• Calcium (pharmacology, physiology)
• Cardiotonic Agents (administration & dosage, chemistry, pharmacokinetics)
• Dihydropyridines (administration & dosage, pharmacokinetics)
• Disease Models, Animal
• Dogs
• Heart Failure (drug therapy, physiopathology)
• Heart Rate (physiology)
• Hydrogen-Ion Concentration
• Injections, Intravenous
• Male
• Myocardial Contraction (drug effects, physiology)
• Myocytes, Cardiac (pathology)
• Pyridazines (administration & dosage, pharmacokinetics)
• Rabbits
• Sarcomeres (drug effects, physiology)
• Stereoisomerism
• Ventricular Function, Left (drug effects, physiology)