FR 173657: A New, Potent, Nonpeptide Kinin B 2 Receptor Antagonist

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Abstract
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.