Linked Life Data

1309870

Source:http://linkedlifedata.com/resource/pubmed/id/1309870

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1992-2-18
pubmed:abstractText
The angiotensin II (AII) antagonist activity of (E)-alpha-[[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5- yl]methylene]-2-thiophenepropanoic acid (SK&F 108566), was examined in a number of in vitro and in vivo assays. In rat and human adrenal cortical membranes, SK&F 108566 displaced specifically bound [125I]AII with IC50 of 9.2 and 3.9 nM, respectively. SK&F 108566 also inhibited [125I]AII binding to human liver membranes (IC50 = 1.7 nM) and to rat mesenteric artery membranes (IC50 = 1.5 nM). In rabbit aortic smooth muscle cells, SK&F 108566 caused a concentration-dependent inhibition of AII-induced increases in intracellular Ca++ levels. In rabbit aortic rings, SK&F 108566 produced parallel rightward shifts in the AII concentration-response curve without affecting the maximal contractile response. Schild analysis of the data yielded a KB value of 0.26 nM and a slope not different from 1, indicative of competition antagonism. SK&F 108566 had no effect on the contractile responses to KCl, norepinephrine or endothelin in rabbit aorta. In conscious normotensive rats, i.v. administration of SK&F 108566 (0.01-0.3 mg/kg) produced dose-dependent parallel shifts in the AII pressor dose-response curve. Administration of SK&F 108566 (3-10 mg/kg) intraduodenally or intragastrically to conscious normotensive rats resulted in a dose-dependent inhibition of the pressor response to AII (250 ng/kg, i.v.). At 10 mg/kg, i.d., significant inhibition of the pressor response to AII was observed for 3 hr. In this same rat model, SK&F 108566 had no effect on base-line pressure or on the pressor response to norepinephrine or vasopressin. The data demonstrate that SK&F 108566 is a potent, highly selective, competitive nonpeptide AII antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
260
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-81
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Pharmacological characterization of the nonpeptide angiotensin II receptor antagonist, SK&F 108566.
pubmed:affiliation
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
pubmed:publicationType
Journal Article, In Vitro