FR167344 free base

FR167344 free base is an orally active, nonpeptide bradykinin receptor B2 antagonist. FR167344 free base shows a high affinity binding to the B2 receptor with an IC₅₀ value of 65 nM and no binding affinity for the B1 receptor. IC50 & Target: IC50: 65 nM (Bradykinin receptor B2)^[1] In Vitro: In competitive experiments using membranes prepared from Chinese hamster ovary cells expressing the bradykinin receptor subtypes, FR167344 shows a high affinity binding to the B2 receptor with IC₅₀ values of 65 nM, and no binding affinity for the B1 receptor. FR167344 inhibits the B2 receptor-mediated phosphatidylinositol (PI) hydrolysis and produces a concentration-dependent rightward shift in the dose-response curve to bradykinin. This shift is accompanied by a progressive reduction of maximal response. Estimated pA2 values for the antagonism of bradykinin induced PI hydrolysis by FR167344 is 8.0. FR167344 shows no stimulatory effects on PI hydrolysis^[1]. In Vivo: Oral administration of FR167344 inhibits carrageenin-induced paw oedema in rats with an ID₅₀ of 2.7 mg/kg at 2h after carrageenin injection. Oral administration of FR167344 inhibits kaolin-induced writhing in mice with an ID₅₀ of 2.8 mg/kg in 10 min writhing and 4.2 mg/kg in 15 min writhing. Oral administration of FR167344 inhibits caerulein-induced pancreatic oedema with an ID₅₀ of 13.8 mg/kg as well as increases in amylase and lipase of blood samples with ID₅₀ of 10.3 and 7.4 mg/kg, respectively, in rats^[2].