HEMODYNAMIC EFFECTS OF 4-(3,4-DIMETHOXYBENZYL)-2-IMIDAZOLIDINONE (Ro 7-2956): A NONADRENERGIC MYOCARDIAL STIMULANT

¹ Department of Pharmacology, Hoffmann-La Roche, Inc., Nutley, New Jersey

The primary cardiovascular actions produced by 4-(3,4-dimethoxybenzyl)-2-imidazolidinone (Ro 7-2956) were a positive inotropic and chronotropic effect and peripheral vasodilation. All of these effects were long lasting. The drug-related cardiac responses were observed in the canine heart-lung preparation, and vasodilation was observed in the canine perfused hind limb. A nine-parameter cardiovascular study in intact dogs showed that the most dominant effect was a marked tachycardia. This marked chronotropic response prevented the hemodynamic expression of the positive inotropic response since stroke index was decreased during the course of drug action. However, Ro 7-2956 effectively reversed three types of failure in the canine heart-lung preparation. The positive inotropic, positive chronotropic and peripheral vasodilator effects did not appear to be mediated through a beta adrenergic mechanism. A significant elevation in blood glucose levels and a nonsignificant increase in blood lactic acid levels were observed, mdicating a drug-related effect on intermediary metabolism.