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-(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.

• Authors: M Asano, C Hatori, N Inamura, H Sawai, J Hirosumi, T Fujiwara, K Nakahara
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 122 Issue 7 Pg. 1436-40 (Dec 1997) ISSN: 0007-1188 [Print] England
• PMID: 9421292 (Publication Type: Journal Article)

Chemical References

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

Topics

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