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

Br J Pharmacol. 1997 Dec;122(7):1436-40. doi: 10.1038/sj.bjp.0701534.

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-(dimethylamin ocarbonyl) 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.

MeSH terms

  • Administration, Oral
  • Animals
  • Antidiarrheals
  • Bradykinin Receptor Antagonists*
  • Carrageenan
  • Ceruletide
  • Disease Models, Animal
  • Excipients
  • Gastrointestinal Agents
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Kaolin
  • Male
  • Mice
  • Mice, Inbred ICR
  • Pain / chemically induced
  • Pain / drug therapy
  • Pancreatitis / chemically induced
  • Pyridines / administration & dosage
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin / drug effects

Substances

  • Antidiarrheals
  • Bradykinin Receptor Antagonists
  • Excipients
  • FR 167344
  • Gastrointestinal Agents
  • Pyridines
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin
  • Kaolin
  • Ceruletide
  • Carrageenan