title: Conformational requirements for dopamine-induced vasodilation.
abstract: The availability of a series of semi-rigid analogs of dopamine and epinine has made it possible to investigate the conformational requirements for action on dopamine and beta2-adrenergic vascular receptors. The analogs were screened for dopamine-agonist action by intra-arterial injections into the renal vascular bed and for beta2-adrenergic activity by similar injections into the femoral vascular bed in dogs pretreated with phenoxybenzamine. 2-Amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN) and its N-methyl derivative (analogous to the trans beta rotamer of dopamine) exhibited pronounced dopamine-agonist activity and minimal beta2-adrenergic activity. In contrast, the semi-rigid analog of the trans alpha rotamer of dopamine (2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene; A-5,6-DTN) and its N-methyl derivative exerted pronounced beta2-adrenergic activity but were inactive as dopamine agonists.6,7-Dihydroxytetrahydroisoquinoline, a semi-rigid analog of the cis beta rotamer of dopamine, did not produce renal vasodilation. These results indicate that a conformation of dopamine similar to that found in A-6,7-DTN is required for dopamine-vascular activity, while the conformation found in A-5,6-DTN is preferred for interaction with beta2-adrenergic receptors.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003846:Deoxyepinephrine / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D007536:Isomerism; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D010643:Phenoxybenzamine; D007545:Isoproterenol; D003846:Deoxyepinephrine; D004298:Dopamine
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