Linked Life Data

10027091

Source:http://linkedlifedata.com/resource/pubmed/id/10027091

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-4-15
pubmed:abstractText
Activation of the kinin-kallikrein system and stimulation of bradykinin (BK) B2 receptors are thought to play an important role in the pathophysiology of inflammation and pain. In the present study, we report the pharmacological properties of a novel nonpeptide bradykinin B2 receptor antagonist, LF 16-0335C, (1-[[3-[(2,4-dimethylquinolin-8-yl) oxymethyl]-2,4-dichloro-phenyl]sulfonyl]-2(S)-[[4-[4- (aminoiminomethyl)-phenylcarbonyl]piperazin-1-yl]carbo nyl]pyrrolidine, 2HCl). In binding studies, LF 16-0335C competed with [3H]bradykinin giving Ki values of 1.65 +/- 0.36 nM and 2.20 +/- 0.30 nM in membrane preparations from rat uterus (RU) and guinea-pig ileum (GPI), respectively. In functional experiments, LF 16-0335C inhibited in a competitive manner BK-induced contractions of both isolated RU and GPI, leading to calculated pA2 values of 7.70 +/- 0.70 and 8.30 +/- 0.30, respectively. The inhibitory effect of LF 16-0335C was fully reversible by washing in the guinea-pig ileum. In vivo, LF 16-0335C given intravenously inhibited in a dose-dependent manner BK-induced hypotension in both animal species, although it was more potent in the guinea-pig than in the rat (ED50, 2.5 +/- 1.6 micrograms/kg versus 22.6 +/- 2.3 micrograms/kg). BK is a potent constrictor of guinea-pig airways and this effect was markedly attenuated by LF 16-0335C. In contrast, LF 16-0335C did not affect histamine- and acetylcholine-induced hypotensive response in the rat. We conclude that LF 16-0335C is a potent and selective nonpeptide B2 receptor antagonist which equally binds to the rat and guinea-pig receptor but displays a different in vivo potency in the two species. Therefore, this drug represents a useful tool to better assess the role of bradykinin in pathophysiological conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0767-3981
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
75-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10027091-Acetylcholine, pubmed-meshheading:10027091-Amidines, pubmed-meshheading:10027091-Animals, pubmed-meshheading:10027091-Binding, Competitive, pubmed-meshheading:10027091-Blood Pressure, pubmed-meshheading:10027091-Bradykinin, pubmed-meshheading:10027091-Dose-Response Relationship, Drug, pubmed-meshheading:10027091-Female, pubmed-meshheading:10027091-Guinea Pigs, pubmed-meshheading:10027091-Histamine, pubmed-meshheading:10027091-Ileum, pubmed-meshheading:10027091-Male, pubmed-meshheading:10027091-Muscle Contraction, pubmed-meshheading:10027091-Piperazines, pubmed-meshheading:10027091-Rats, pubmed-meshheading:10027091-Receptor, Bradykinin B2, pubmed-meshheading:10027091-Receptors, Bradykinin, pubmed-meshheading:10027091-Tritium, pubmed-meshheading:10027091-Uterus, pubmed-meshheading:10027091-Vasodilator Agents
pubmed:year
1999
pubmed:articleTitle
In vitro and in vivo effects of the new nonpeptide bradykinin B2 receptor antagonist, LF 16-0335C, on guinea-pig and rat kinin receptors.
pubmed:affiliation
Groupe de Pharmacochimie des Récepteurs, Centre de Recherche, Laboratoires Fournier, Daix, France.
pubmed:publicationType
Journal Article, In Vitro