Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1997-5-22
|
| pubmed:abstractText |
1. An orally active, nonpeptide bradykinin (BK) B2 receptor antagonist, FR173657 (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2-4-dichloro-3-[(2-methyl-8-quinolin yl) oxymethyl]phenyl]-N-methylaminocarbonyl-methyl] acrylamide) has been identified. 2. This compound displaced [3H]-BK binding to B2 receptors present in guinea-pig ileum membranes with an IC50 of 5.6 x 10(-10) M and in rat uterus with an IC50 of 1.5 x 10(-9) M. It did not inhibit different specific radio-ligand binding to other receptor sites. 3. In human lung fibroblast IMR-90 cells, FR173657 displaced [3H]-BK binding to B2 receptors with an IC50 of 2.9 x 10(-9) M and a Ki of 3.6 x 10(-10) M, but did not reduce [3H]-des]Arg10-kallidin binding to B1 receptors. 4. In guinea-pig isolated preparations, FR173657 antagonized BK-induced contractions with an IC50 of 7.9 x 10(-9) M, but did not antagonize acetylcholine or histamine-induced contractions even at a concentration of 10(-6) M. FR173657 caused parallel rightward shifts of the concentration-response curves to BK at concentrations of 10(-9) M and 3.2 x 10(-9) M, and a little depression of the maximal response in addition to the parallel rightward shift of the concentration-response curve at a concentration of 10(-8) M. Analysis of the data yield a pA2 of 9.2 +/- 0.2 (n = 5) and a slope of 1.5 +/- 0.2 (n = 5). 5. In vivo, the oral administration of FR173657 inhibited BK-induced bronchoconstriction dose-dependently in guinea-pigs with an ED50 of 0.075 mg kg-1, but did not inhibit histamine-induced bronchoconstriction even at 1 mg kg-1. FR173657 also inhibited carrageenin-induced paw oedema with an ED50 of 6.8 mg kg-1 2 h after the carrageenin injection in rats. 6. These results show that FR173657 is a potent, selective, and orally active bradykinin B2 receptor antagonist.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0007-1188
|
| pubmed:author |
pubmed-author:AbeYY,
pubmed-author:AsanoMM,
pubmed-author:FujiwaraTT,
pubmed-author:HatoriCC,
pubmed-author:InamuraNN,
pubmed-author:InoueTT,
pubmed-author:KatayamaAA,
pubmed-author:KayakiriHH,
pubmed-author:NakaharaKK,
pubmed-author:OkaHH,
pubmed-author:OkuharaMM,
pubmed-author:SatohSS,
pubmed-author:SawadaYY,
pubmed-author:SawaiHH
|
| pubmed:issnType |
Print
|
| pubmed:volume |
120
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
617-24
|
| pubmed:dateRevised |
2008-11-20
|
| pubmed:meshHeading |
pubmed-meshheading:9051299-Administration, Oral,
pubmed-meshheading:9051299-Animals,
pubmed-meshheading:9051299-Bradykinin,
pubmed-meshheading:9051299-Bronchoconstriction,
pubmed-meshheading:9051299-Cells, Cultured,
pubmed-meshheading:9051299-Dose-Response Relationship, Drug,
pubmed-meshheading:9051299-Female,
pubmed-meshheading:9051299-Guinea Pigs,
pubmed-meshheading:9051299-Humans,
pubmed-meshheading:9051299-Ileum,
pubmed-meshheading:9051299-Inflammation,
pubmed-meshheading:9051299-Male,
pubmed-meshheading:9051299-Muscle, Smooth,
pubmed-meshheading:9051299-Quinolines,
pubmed-meshheading:9051299-Rats,
pubmed-meshheading:9051299-Rats, Sprague-Dawley,
pubmed-meshheading:9051299-Receptor, Bradykinin B2,
pubmed-meshheading:9051299-Receptors, Bradykinin,
pubmed-meshheading:9051299-Uterus
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
The identification of an orally active, nonpeptide bradykinin B2 receptor antagonist, FR173657.
|
| pubmed:affiliation |
Department of Pharmacology, Fujisawa Pharmaceutical Co, Ltd., Ibaraki, Japan.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|