Document Detail

Effects of ring fluorination on the cardiovascular actions of dopamine and norepinephrine in the dog.
MedLine Citation:
PMID:  6894165     Owner:  NLM     Status:  MEDLINE    
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.
L I Goldberg; J D Kohli; D Cantacuzene; K L Kirk; C R Creveling
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
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:
Created Date:  1981-05-26     Completed Date:  1981-05-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  509-13     Citation Subset:  IM    
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MeSH Terms
Blood Pressure / drug effects
Dopamine / analogs & derivatives*,  pharmacology
Hemodynamics / drug effects*
Myocardial Contraction / drug effects
Norepinephrine / analogs & derivatives*,  pharmacology
Regional Blood Flow / drug effects
Renal Artery
Structure-Activity Relationship
Vasodilation / drug effects
Grant Support
Reg. No./Substance:
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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