title: Antagonistic effects of FR 173657 on human, pig, rabbit, and guinea pig kinin receptors: an in vitro study.
abstract: The pharmacodynamic features of the new nonpeptide kinin B2 receptor antagonist FR 173657 were evaluated on pig, rabbit, guinea pig, and human native kinin B2 receptors. FR 173657 exerted high antagonistic activity in all preparations examined. In particular, it acts as a competitive antagonist in the rabbit jugular vein (pA2 8.9) and in the human umbilical vein (pA2 8.2) but as a noncompetitive antagonist in the pig coronary artery (pKB 9.2) and in the guinea pig ileum (pKB 9.2) stimulated with the selective B2 receptor agonist bradykinin (BK). In contrast, FR 173657 failed to antagonize the biological effects of the selective B1 receptor agonist LysdesArg9BK in the pig renal vein, rabbit aorta, and human umbilical vein, three kinin B1 receptor systems. Moreover, this compound was inactive against the effects induced by noradrenaline, 5-hydroxytryptamine, endothelin-1, angiotensin II, substance P, acetylcholine, and histamine in the B2 receptor preparations. Taken together, these results demonstrate that FR 173657 is the first potent nonpeptide B2 receptor antagonist with high affinity, selectivity, and specificity for kinin B2 receptors of different species, including man.
authors.affiliation: Institute of Pharmacology, University of Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rizzi
authors.forename: F
authors.initials: F
authors.lastname: Gobeil
authors.forename: G
authors.initials: G
authors.lastname: Bogoni
authors.forename: G
authors.initials: G
authors.lastname: Calò
authors.forename: C
authors.initials: C
authors.lastname: Campobasso
authors.forename: N
authors.initials: N
authors.lastname: Inamura
authors.forename: D
authors.initials: D
authors.lastname: Regoli
mesh_terms: D000328:Adult; D000818:Animals; D001667:Binding, Competitive; D003331:Coronary Vessels / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000648:ultrastructure; D066298:In Vitro Techniques; D007601:Jugular Veins / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors*; D013045:Species Specificity; D013552:Swine
chemical_list: C105311:FR 173657; D011804:Quinolines; D018042:Receptors, Neurokinin-3