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Cardiovascular pharmacology of the cardiotonic, imazodan (Cl‐914)
Author(s) -
Evans D.B.,
Potoczak R.E.,
Steffen R.P.,
Burmeister W.E.,
McNish R.W.,
Schenden J.A.,
Kaplan H.R.
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430090207
Subject(s) - contractility , inotrope , propranolol , chronotropic , vasodilation , coronary vasodilator , perfusion , medicine , blood pressure , heart rate , pharmacology , papillary muscle , endocrinology
Imazodan is a novel pyridazinone derivative. It was evaluated in excised cardiac tissue, anesthetized dogs and monkeys, and conscious dogs. Imazodan, 10 −5 –10 −3 M, produced dose‐dependent increases in guinea pig atrial and rabbit papillary muscle contractility. In ansthetized dogs and rhesus monkeys, imazodan, 0.001–1.0 mg/kg IV, produced dosedependent increases of 10–150% in myocardial contractility (dP/dt max of left ventricular pressure), and decreases of 1–31% in aortic blood pressure. Heart rate increases were minimal (0–34%) in comparison to the changes in contractility and they occurred only at the higher doses. The positive inotropic action of imazodan was not blocked by β‐adrenoceptor blockade with propranolol. Forelimb perfusion studies in the anesthetized dog demonstrated that imazodan produces a dose‐dependent direct peripheral vasodilator action. This agent was also demonstrated to be a highly effective cardiotonic when administered orally (0.1–1.0 mg/kg) to conscious dogs. The results of these studies indicate that imazodan is an orally effective cariotonic that possesses balanced positive inotrophic and peripheral vasodilator activities and possesses a wide margin of cardiac safety.