Effects of a nonpeptide bradykinin B2receptor antagonist, FR167344, on differentin vivoanimal models of inflammation

Autor: Hiroe Sawai, Kunio Nakahara, Chie Hatori, Jiro Hirosumi, Masayuki Asano, Noriaki Inamura, Tatsujiro Fujiwara
Rok vydání: 1997
Předmět:
Zdroj: British Journal of Pharmacology. 122:1436-1440
ISSN: 0007-1188
Popis: 1 The effects of a novel, potent and orally active nonpeptide bradykinin B2 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. 2 Oral administration of FR167344 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 oedema 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, respectively, in rats (n=10). 5 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 B2 receptors in various in vivo models of inflammation.
Databáze: OpenAIRE
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