FR 173657: A new, potent, nonpeptide kinin B-2 receptor antagonist - An in vitro study

被引：41

作者：

Rizzi, A

Gobeil, F

Calo, G

Inamura, N

Regoli, D

机构：

[1] UNIV FERRARA, INST PHARMACOL, I-44100 FERRARA, ITALY

[2] UNIV SHERBROOKE, SCH MED, DEPT PHARMACOL, SHERBROOKE, PQ J1K 2R1, CANADA

[3] FUJISAWA PHARMACEUT CO LTD, OSAKA 532, JAPAN

来源：

HYPERTENSION | 1997年 / 29卷 / 04期

关键词：

FR; 173657; receptors; bradykinin; blood vessels; species specificity; biological assay;

D O I：

10.1161/01.HYP.29.4.951

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

FR 173657, the first effective nonpeptide kinin B-2 receptor antagonist, has been tested in four preparations from different species (human, pig, rabbit, and guinea pig). The new compound shows high apparent affinity for the four B-2 receptors, with pA(2) values ranging from 8.2 to 9.4. FR 173657 is a selective B-2 receptor antagonist that does not interact with human, pig, or rabbit B-1 receptors. The new compound is extremely specific for the kinin B-2 receptors as it does not affect the myotropic effects of norepinephrine, endothelin-1, or 5-hydroxytryptamine in the human umbilical vein; the contractions elicited by substance P and angiotensin II in the rabbit jugular vein or those produced by acetylcholine and histamine in the guinea pig ileum; or the relaxation of the pig coronary artery induced by norepinephrine and substance P. FR 173657 acts as a competitive antagonist over an extended range of concentrations on human and rabbit B-2 receptors, whereas on pig and guinea pig receptors, it depresses the maximal effect of bradykinin and thus appears to act as a noncompetitive antagonist.

引用

页码：951 / 956

页数：6

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