INHIBITION OF THE RESPONSE TO NASAL PROVOCATION WITH BRADYKININ BY HOE-140 - EFFICACY AND DURATION OF ACTION

The present studies were undertaken as a first step to evaluate the po tential usefulness of the bradykinin antagonist HOE-140 in delineating the role of kinins in the pathogenesis of chronic rhinitis. Intranasa l single-dose administration of HOE-140, at doses up to 500 mu g, was safe and well tolerated. Bradykinin-induced symptoms and increased vas cular permeability could be inhibited, in a dose-dependent manner, by preadministration of HOE-140 5 min prior to kinin challenge. The resul ts of dose-ranging experiments suggested that bradykinin and HOE-140 w ere approximately equipotent at bradykinin receptors. Preadministratio n of HOE-140 2 h before kinin challenge caused a significant but much weaker level of inhibition than that seen with 5-min preadministration . Comparison of data with those obtained during dose-ranging studies s uggested that more than 90% of the administered HOE-140 was lost durin g this 2-h period. We conclude that topical HOE-140 is an effective in hibitor of the effects of bradykinin on the nasal mucosa but that the short duration of action of this drug may severely limit the utility o f HOE-140 in delineating the role of kinins in the pathogenesis of chr onic rhinitis.