Effects of a nonpeptide bradykinin B 2 receptor antagonist, FR167344, on different in vivo animal models of inflammation

• Published in: British journal of pharmacology Vol. 122; no. 7; pp. 1436 - 1440
• Main Authors: Asano, Masayuki, Hatori, Chie, Inamura, Noriaki, Sawai, Hiroe, Hirosumi, Jiro, Fujiwara, Tatsujiro, Nakahara, Kunio
• Format: Journal Article
• Language: English
• Published: 12-02-2009
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701534

The effects of a novel, potent and orally active nonpeptide bradykinin B
2
receptor antagonist, FR167344 (N ‐[N ‐[3 ‐[(3 ‐ bromo‐ 2 ‐methylimidazo[1,2‐a]pyridin‐8‐yl)oxymethyl]‐2,4‐dichlorophenyl]‐N‐methylaminocarbonylmethyl]‐4‐(dimethylaminocarbonyl) cinnamylamide hydrochloride) were tested in three different
in vivo
models of inflammation.
Oral administration of FR167344 inhibited carrageenin‐induced paw oedema in rats (carrageenin: 1%, 0.1 ml per animal, intraplantar), with an ID
50
of 2.7 mg kg
−1
at 2 h after carrageenin injection (
n
=10 or 11).
Oral administration of the compound also inhibited kaolin‐induced writhing (kaolin: 250 mg kg
−1
, i.p.) in mice, with ID
50
of 2.8 mg kg
−1
in 10 min writhing and 4.2 mg kg
−1
in 15 min writhing (
n
=19 or 20).
Additionally, oral administration of FR167344 inhibited caerulein‐induced pancreatic oedema with an ID
50
of 13.8 mg kg
−1
as well as increases in amylase and lipase of blood samples with ID
50
of 10.3 and 7.4 mg kg
−1
, respectively, in rats (
n
=10).
These results show that FR167344 is an orally active, anti‐inflammatory and anti‐nociceptive agent in carrageenin‐induced paw oedema, kaolin‐induced writhing and caerulein‐induced pancreatitis. FR167344 may have therapeutic potential against inflammatory diseases by oral administration and it may be a useful tool for studying the involvement of B
2
receptors in various
in vivo
models of inflammation.