Pharmacological evaluation of a selective bradykinin B antagonist in a canine model of arthritis.

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 B receptor 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 B receptor during an acute inflammatory model of pain, indicates an inability of the receptor to mediate inflammatory pain in canines.