Effects of a nonpeptide bradykinin B₂ receptor antagonist, FR167344, on different in vivo animal models of inflammation

Abstract

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.

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