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Journal of Pharmacology And Experimental Therapeutics, Vol. 161, Issue 2, 247-261, 1968
Copyright © 1968 by American Society for Pharmacology and Experimental Therapeutics

SOME EFFECTS OF IPROVERATRIL (ISOPTIN) ON THE CARDIOVASCULAR SYSTEM

W. G. Nayler 1, I. McInnes 1, J. B. Swann 1, J. M. Price 1, V. Carson 1, D. Race 1, and T. E. Lowe 1

1 The Baker Medical Research Institute, Melbourne, Australia

The effect of iproveratril (agr-isopropyl-agr[N-methyl-N-homoveratryl]-ggr-aminopropyl-3,4-dimethoxyphenol acetonitrile hydrochloride; Isoptin; Verpamil) on the cardiovascular system was investigated using intact rabbits, Langendorff-perfused rat hearts, dog papillary muscles and dog heart-lung bypass preparations. In intact rabbits 0.1 to 0.5 mg/kg of iproveratril caused hypotension and bradycardia; after iproveratril the infusion of isoproterenol caused an increase in pulse pressure and heart rate, and a slight rise in systemic blood pressure. In isolated rat hearts 0.1 to 0.5 µg/ml of iproveratril depressed and slowed the contractions, but the subsequent addition of isoproterenol produced positive inotropic and chronotropic responses and an increase in the percentage of phosphorylase enzyme in the a form, indicating the absence of beta adrenergic blockade. Iproveratril, 0.05 to 03 mg/kg, displaced dog left ventricular "work" function curves to the right and exerted a negative inotropic effect on isolated papillary muscles. These changes were reversed by isoproterenol. In the peripheral circulation iproveratril caused vasodilation. In the presence of iproveratril isoproterenol failed to produce further vasodilation, whereas eledoisin did so. Iproveratril consistently reduced the resistance blood flow in the coronary circulation; it did not block the cardiac effect of stellate ganglion stimulation. These results are interpreted to mean that the negative inotropic and chronotropic effect of iproveratril on heart muscle does not reflect beta adrenergic blockade and that this drug may produce beta adrenergic blockade in the peripheral circulation only. The effects of iproveratril on the cardiovascular system were not modified by the prior administration of propantheline, reserpine or beta adrenergic blocking drugs.

Submitted on October 17, 1967
Accepted on February 2, 1968




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