M. Asano et al., EFFECTS OF A NONPEPTIDE BRADYKININ B-2 RECEPTOR ANTAGONIST, FR167344,ON DIFFERENT IN-VIVO ANIMAL-MODELS OF INFLAMMATION, British Journal of Pharmacology, 122(7), 1997, pp. 1436-1440
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.