| Effects of ring fluorination on the cardiovascular actions of dopamine and norepinephrine in the dog. | |
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MedLine Citation:
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PMID: 6894165 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The 2-, 5- and 6-fluoro (F) analogs of dopamine (DA) and (+/-)-norepinephrine (NE) were compared with the respective parent molecules for alpha, beta-1 and beta-2 adrenergic and vascular DA activities in pentobarbital-anesthetized dogs. 2-F and 5-F DA were equipotent while 6-F DA was about 4-fold less active than DA in causing renal vasodilation in phenoxybenzamine pretreated dogs (vascular DA activity). The three analogs were indistinguishable from DA for vasoconstrictor activity in the femoral vascular bed (alpha adrenergic activity). 2-F and 6-F DA were equipotent to DA while 5-F was about 2-fold more active than DA in inotropic activity (beta-1 adrenergic activity). In contrast, F NE analogs showed marked differential activities. 2-F NE resembled isoproterenol in increasing cardiac contractility, lowering diastolic blood pressure and causing vasodilation in the femoral vascular bed. The 5-F analog was the most potent for (beta-1 adrenergic activity and produced biphasic effects on blood pressure and the femoral vascular bed. 6-F NE exerted no inotropic activity in dose 50- to 80-fold higher than the threshold dose of l-NE and caused vasoconstriction. Thus, fluorine substitution in either of the three positions in the benzene ring of DA induced only minor, if any, differences in receptor activation when compared with DA. On the other hand, fluorine substitution in the benzene ring of NE yielded compounds with marked differential receptor activity. These data indicate that the differences between the effects of F substitution on DA and NE analogs must be related to the only structural difference between the two catecholamines, the presence of a beta-hydroxyl group in NE. |
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Authors:
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L I Goldberg; J D Kohli; D Cantacuzene; K L Kirk; C R Creveling |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 213 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1980 Jun |
Date Detail:
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Created Date: 1981-05-26 Completed Date: 1981-05-26 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 509-13 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects Dogs Dopamine / analogs & derivatives*, pharmacology Female Hemodynamics / drug effects* Male Myocardial Contraction / drug effects Norepinephrine / analogs & derivatives*, pharmacology Regional Blood Flow / drug effects Renal Artery Structure-Activity Relationship Vasodilation / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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GM-22220/GM/NIGMS NIH HHS; NS-12324/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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404-84-2/2-fluorodopamine; 51-41-2/Norepinephrine; 59043-70-8/6-fluorodopamine; 71144-39-3/5-fluorodopamine; 71144-40-6/3-fluoronorepinephrine; 86820-21-5/6-fluoronorepinephrine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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