title: Pharmacological evaluation of a selective bradykinin B1antagonist in a canine model of arthritis.
abstract: The effects of a selective bradykinin 1 receptor antagonist, compound A, were evaluated in a canine model of acute inflammatory model of arthritis. Despite detection of the B1receptor in canine type B synoviocytes using a fluorescent ligand, oral administration of compound A (9 and 27 mg/kg) did not improve weight bearing of dogs injected intra-articularly with IL-1β in a force plate analysis. Analysis of the synovial fluid of IL-1β-treated dogs indicated high levels of bradykinin postchallenge. Excellent exposure, coupled with evidence of the presence of the B1receptor during an acute inflammatory model of pain, indicates an inability of the receptor to mediate inflammatory pain in canines.
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Duclos
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Rugg
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: White
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Ross
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Darling
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: D
authors.initials: D
authors.lastname: Huczek
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Curry
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Alexander-Bowman
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Townley
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: D
authors.initials: D
authors.lastname: Garcia-Tapia
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chio
authors.affiliation: Global Therapeutics Research, Zoetis, Kalamazoo, MI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kamerling
mesh_terms: D000818:Animals; D001168:Arthritis / Q000188:drug therapy / Q000662:veterinary*; D065169:Bradykinin B1 Receptor Antagonists / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D008297:Male; D009536:Niacinamide / Q000032:analysis / Q000494:pharmacology*; D043783:Receptor, Bradykinin B1 / Q000032:analysis; D000070918:Synoviocytes / Q000737:chemistry
chemical_list: C000621164:5-amino-N-(3-((4-((4-methoxy-2-(trifluoromethyl)phenyl)amino)benzyl)carbamoyl)tetrahydrofuran-3-yl)nicotinamide; D065169:Bradykinin B1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D009536:Niacinamide