Departmental Bulletin Paper Actions of a New Cardiotonic Agent, SCH00013, on Guinea-pig Heart

齊藤, 久美子  ,  酒井 淳一  ,  堀田 芳弘

 A new cardiotonic agent, SCH00013 (SCH), which was synthesized by Zenyaku Kogyo Company, Limited, exhibits cardiotonic effects by enhancing calcium sensitivity [1]. In this study, we examined the inotropic and chronotropic effects of SCH usin right atrial muscles extirpated from guinea pigs. Although 10 - 4 M SCH showed positive inotropic effects (50% of those of noradrenaline (NAd)), there was no increase in the heart rate. In addition, we measured changes in the left ventricular diastolic pressure (LVDP) and transient Ca 2 + (TCa) signals in Fura-2-loaded Langendorff hearts. The administration of 10 -5 M SCH decreased the level of TCa, whereas 10 - 4 M SCH administration increased it. On the other hand, pimobendan (PIM), which is used as a drug for heart failure due to its calcium sensitivity-enhancing actions, decreased the level of TCa at 10 - 4 M despite an increase in contractility. This suggests that the mechanism of Ca 2+ contractile protein system sensitivity differs between SCH and PIM. As SCH does not increase the heart rate in the presence of heart failure, it may protect the cardiac muscle.

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