Document Detail


SK&F 87516, a close analog of fenoldopam, is a partial agonist at dopamine-1 and alpha-2 receptors and produces stimulation of 5-hydroxytryptamine-2 receptors in the cardiovascular system of the rat.
MedLine Citation:
PMID:  1672375     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In pentobarbital-anesthetized rats, SK&F 87516 (1.25-80 micrograms/kg/min intravenously over 15 min), the fluoro analog of the selective DA-1 dopamine receptor agonist fenoldopam produced dose-related decreases in carotid artery blood pressure that faded during the infusion period. These effects were abolished by SCH 23390, prolonged by ritanserin, but unchanged by bilateral vagotomy, atenolol, ICI 118,551, idazoxan, methylatropine or S-sulpiride. SK&F 87516 also inhibited the hypotensive effects of clonidine and of the DA-1 receptor agonist fenoldopam, but not of acetylcholine. In pithed rats, SK&F 87516 produced a biphasic vasopressor response. The initial phase was enhanced by SCH 23390 and converted to a transient hypotension by idazoxan. The secondary response was inhibited by ritanserin and enalapril. In pithed, but not in intact rats, SK&F 87516 increased plasma renin activity. In intact rats, SK&F 87516 produced dose-related bradycardic effects that were inhibited (50%) by idazoxan, methylatropine or bilateral vagotomy and abolished by chlorisondamine or pithing. In pithed rats pretreated with either saline or idazoxan, SK&F 87516 reduced the tachycardia to electrical stimulation of preganglionic more than that to postganglionic cardioaccelerator nerve fibers. However, it did not modify heart rate increases evoked by intravenous norepinephrine. In conclusion, SK&F 87516 produces hypotension via vascular DA-1 receptor stimulation. The fading of this effect during the infusion of SK&F 87516 may be related to the partial agonist property of this compound at DA-1 receptors and the stimulation of 5-hydroxytryptamine-2 receptors. SK&F 87516 also behaves as a partial agonist at alpha-2 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
A C Le Monnier de Gouville; K Lawson; C Thiry; I Cavero
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  256     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1991 Mar 
Date Detail:
Created Date:  1991-04-24     Completed Date:  1991-04-24     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:  1049-56     Citation Subset:  IM    
Affiliation:
Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
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MeSH Terms
Descriptor/Qualifier:
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / administration & dosage,  analogs & derivatives*,  pharmacokinetics,  pharmacology
Animals
Cardiovascular System / drug effects*
Dopamine Agents / administration & dosage,  pharmacokinetics,  pharmacology*
Fenoldopam
Hemodynamics / drug effects
Infusions, Intravenous
Injections, Intravenous
Male
Norepinephrine / blood
Rats
Receptors, Dopamine / drug effects*
Receptors, Serotonin / drug effects*
Renin / blood
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/Dopamine Agents; 0/Receptors, Dopamine; 0/Receptors, Serotonin; 0/Vasodilator Agents; 51-41-2/Norepinephrine; 67227-56-9/Fenoldopam; 67287-49-4/2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; 72912-26-6/SK&F R87516; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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