EFFECTS OF A NONPEPTIDE BRADYKININ B-2 RECEPTOR ANTAGONIST, FR167344,ON DIFFERENT IN-VIVO ANIMAL-MODELS OF INFLAMMATION

1 The effects of a novel: potent and orally active nonpeptide bradykin in B-2 receptor antagonist, FR167344 thylaminocarbonylmethyl]-4-(dimet hylaminocarbonyl) cinnamylamide hydrochloride) were tested in three di fferent in who models of inflammation. 2 Oral administration of FR1673 44 inhibited carrageenin-induced paw oedema in rats (carrageenin: 1%, 0.1 ml per animal, intraplantar), with an ID50 of 2.7 mg kg(-1) at 2 h after carrageenin injection (n = 10 or 11). 3 Oral administration of the compound also inhibited kaolin-induced writhing (kaolin: 250 mg kg (-1), i.p.) in mice, with ID50 of 2.8 mg kg(-1) in 10 min writhing and 4.2 mg kg(-1) in 15 min writhing (n = 19 or 20). 4 Additionally, oral administration of FR167344 inhibited caerulein-induced pancreatic oed ema with an ID50 of 13.8 mg kg(-1) as well as increases in amylase and lipase of blood samples with ID50 of 10.3 and 7.4 mg kg(-1), respecti vely, in rats (n = 10). 5 These results show that FR167344 is an orall y active, anti-inflammatory and anti-nociceptive agent in carrageenin- induced paw oedema, kaolin-induced writhing and caerulein-induced panc reatitis. FR167344 may have therapeutic potential against inflammatory diseases by oral administration and it may be a useful tool for study ing the involvement of Bt receptors in various in vivo models of infla mmation.