Publication

Direct vasodilating effects of the new dopaminergic agonist Z1046 in human arteries

Teisman, ACH., Buikema, H., van Veldhuisen, FJ., de Zeeuw, D. & van Gilst, WH., Apr-2000, In : Journal of Cardiovascular Pharmacology. 35, 4, p. 581-585 5 p.

Research output: Contribution to journalArticleAcademicpeer-review

Dopaminergic agonists remain of interest in the treatment of heart failure; however, concomitant stimulation of alpha- and beta-receptors should be avoided. This study evaluates the dopaminergic and adrenergic (vasodilating) properties of Z1046, epinine (the active metabolite of ibopamine), and dopamine. Isotonic contraction experiments were performed on human internal mammary artery rings in vitro. alpha(1)-Antagonistic effects of Z1046 were demonstrated 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 dopamine were studied by performing cumulative dose-response relations both at baseline and in precontracted artery rings both with and without the D-1-like antagonist SCH23390. In contrast to both epinine and dopamine, Z1046 is devoid of alpha(1)-receptor-mediated contraction. Furthermore, Z1046, epinine, and dopamine induced direct dopamine receptor-mediated vasodilation when interfering alpha(1) effects were blocked. In contrast to epinine and dopamine, Z1046 is devoid of vasoconstricting properties at higher dosages. Because of its D-1-like agonistic and alpha(1)- antagonistic properties, Z1046 is an effective vasodilator in the whole dosage range. Because of its total receptor profile, Z1046 appears to be more favorable for treatment of heart failure than is ibopamine.

Original languageEnglish
Pages (from-to)581-585
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume35
Issue number4
Publication statusPublished - Apr-2000

    Keywords

  • epinine, dopamine, Z1046, human arteries, DA1 RECEPTOR AGONIST, HEART-FAILURE, IBOPAMINE, VASCULATURE, FENOLDOPAM

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