Direct vasodilating effects of the new dopaminergic agonist Z1046 in humanarteries

Dopaminergic agonists remain of interest in the treatment of heart failure; however, concomitant stimulation of alpha- and beta-receptors should be av oided. This study evaluates the dopaminergic and adrenergic (vasodilating) properties of Z1046, epinine (the active metabolite of ibopamine), and dopa mine. Isotonic contraction experiments were performed on human internal mam mary artery rings in vitro. alpha(1)-Antagonistic effects of Z1046 were dem onstrated by performing cumulative dose-response curves with the selective alpha(1)-agonist phenylephrine in the presence of Z1046. Furthermore, both alpha(1)- and dopamine-mediated receptor effects of Z1046, epinine, and dop amine were studied by performing cumulative dose-response relations both at baseline and in precontracted artery rings both with and without the D-1-l ike antagonist SCH23390. In contrast to both epinine and dopamine, Z1046 is devoid of alpha(1)-receptor-mediated contraction. Furthermore, Z1046, epin ine, and dopamine induced direct dopamine receptor-mediated vasodilation wh en interfering alpha(1) effects were blocked. In contrast to epinine and do pamine, Z1046 is devoid of vasoconstricting properties at higher dosages. B ecause of its D-1-like agonistic and alpha(1)- antagonistic properties, Z10 46 is an effective vasodilator in the whole dosage range. Because of its to tal receptor profile, Z1046 appears to be more favorable for treatment of h eart failure than is ibopamine.