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(Hypertension. 1997;29:951-956.)
© 1997 American Heart Association, Inc.

Articles

FR 173657: A New, Potent, Nonpeptide Kinin B₂ Receptor Antagonist

An In Vitro Study

Anna Rizzi; Fernand Gobeil; Girolamo Calò; Noriaki Inamura; ; Domenico Regoli

From the Institute of Pharmacology, University of Ferrara (Italy) (A.R., G.C., D.R.,); Department of Pharmacology, Medical School, University of Sherbrooke (Canada) (F.G.); and Fujisawa Pharmaceutical Co, Osaka, Japan (N.I.).

Correspondence to Prof Domenico Regoli, Institute of Pharmacology, University of Ferrara, Via Fossato di Mortara, 17-19, 44100 Ferrara, Italy. E-mail fmc{at}ifeuniv.unife.it

Abstract FR 173657, the first effective nonpeptide kinin B₂ 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 B₂ receptors, with pA₂ values ranging from 8.2 to 9.4. FR 173657 is a selective B₂ receptor antagonist that does not interact with human, pig, or rabbit B₁ receptors. The new compound is extremely specific for the kinin B₂ 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 B₂ receptors, whereas on pig and guinea pig receptors, it depresses the maximal effect of bradykinin and thus appears to act as a noncompetitive antagonist.

Key Words: FR 173657 • receptors, bradykinin • blood vessels • species specificity • biological assay

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