Pharmacology of LY195115, a Potent, Orally Active Cardiotonic with a Long Duration of Action

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Abstract
Compound LY195115 is a novel cardiotonic with both inotropic and vasodilator activities. In cat papillary muscles, LY195115 increased contractility in a concentration-dependent manner; its actions were not blocked by either prazosin or propranolol. An intravenous dose of 7.0 .mu.g/kg LY195115 resulted in a 50% increase in contractility in anesthetized dogs; comparable inotropic responses were observed in anesthetized cats receiving 10 .mu.g/kg i.v. These doses of LY195115 increased heart rates of both dogs and cats by 5.0 .mu.g/kg decreased left ventricular end-diastolic pressure and systemic vascular resistance; mean arterial blood pressure and cardiac output were unchanged. Estimated myocardial oxygen consumption (heart rate times either systolic or mean arterial blood pressure) was not altered by doses as high as 110 .mu.g/kg. This balance of inotropic/vasodilator activities while maintaining myocardial oxygen supply/demand.