FR-173657 - A NEW, POTENT, NONPEPTIDE KININ B-2 RECEPTOR ANTAGONIST -AN IN-VITRO STUDY

FR 173657, the first effective nonpeptide kinin B-2 receptor antagonis t, has been tested in four preparations from different species (human, pig, rabbit, and guinea pig). The new compound shows high apparent af finity 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 i s extremely specific for the kinin B-2 receptors as it does not affect the myotropic effects of norepinephrine, endothelin-1, or 5-hydroxytr yptamine in the human umbilical vein; the contractions elicited by sub stance P and angiotensin II in the rabbit jugular vein or those produc ed by acetylcholine and histamine in the guinea pig ileum; or the rela xation of the pig coronary artery induced by norepinephrine and substa nce P. FR 173657 acts as a competitive antagonist over an extended ran ge of concentrations on human and rabbit B-2 receptors, whereas on pig and guinea pig receptors, it depresses the maximal effect of bradykin in and thus appears to act as a noncompetitive antagonist.