Pharmacological evaluation of a selective bradykinin Bantagonist 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 Breceptor 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 Breceptor during an acute inflammatory model of pain, indicates an inability of the receptor to mediate inflammatory pain in canines.