title: 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.affiliation: Department of Pharmacology, Exploratory Research Laboratories, Fujisawa Pharmaceutical, Tsukuba, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: C
authors.initials: C
authors.lastname: Hatori
authors.forename: N
authors.initials: N
authors.lastname: Inamura
authors.forename: H
authors.initials: H
authors.lastname: Sawai
authors.forename: J
authors.initials: J
authors.lastname: Hirosumi
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: K
authors.initials: K
authors.lastname: Nakahara
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000930:Antidiarrheals; D065168:Bradykinin Receptor Antagonists; D002351:Carrageenan; D002108:Ceruletide; D004195:Disease Models, Animal; D005079:Excipients; D005765:Gastrointestinal Agents; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007616:Kaolin; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010195:Pancreatitis / Q000139:chemically induced; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects
chemical_list: D000930:Antidiarrheals; D065168:Bradykinin Receptor Antagonists; D005079:Excipients; C106745:FR 167344; D005765:Gastrointestinal Agents; D011725:Pyridines; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D007616:Kaolin; D002108:Ceruletide; D002351:Carrageenan