title: Direct vasodilating effects of the new dopaminergic agonist Z1046 in human arteries.
abstract: 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. alpha1-Antagonistic effects of Z1046 were demonstrated by performing cumulative dose-response curves with the selective alpha1-agonist phenylephrine in the presence of Z1046. Furthermore, both alpha1- 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 D1-like antagonist SCH23390. In contrast to both epinine and dopamine, Z1046 is devoid of alpha1-receptor-mediated contraction. Furthermore, Z1046, epinine, and dopamine induced direct dopamine receptor-mediated vasodilation when interfering alpha1 effects were blocked. In contrast to epinine and dopamine, Z1046 is devoid of vasoconstricting properties at higher dosages. Because of its D1-like agonistic and alpha1-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.
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, The Netherlands. cliphar@med.rug.nl
authors.forename: A C
authors.initials: AC
authors.lastname: Teisman
authors.forename: H
authors.initials: H
authors.lastname: Buikema
authors.forename: D J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: D
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: W H
authors.initials: WH
authors.lastname: van Gilst
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003846:Deoxyepinephrine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects*; D008875:Middle Aged; D009284:Naphthols / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018491:Dopamine Agonists; D009284:Naphthols; D014665:Vasodilator Agents; C105333:Z1046; D003846:Deoxyepinephrine; D004298:Dopamine