Effect of novel selective non-peptide kinin B1 receptor antagonists on mouse pleurisy induced by carrageenan

Two novel selective non-peptide kinin B-1 receptor antagonists, the benzodiazepine antagonist and SSR240612, were evaluated in carrageenan-induced mouse pleurisy. The peptide 8715 (0.5 mg/kg, i.p.) and the non-peptide benzodiazepine (3 mg/kg, i.p.) antagonists significantly decreased cellular migration (predominantly neutrophils), without altering plasma exudation. SSR240612 (1 mg/kg, i.p.) diminished total cells and neutrophils, besides exudation. Oral administration of SSR240612 (10 mg/kg) also reduced total cell and neutrophil counts. Only the benzodiazepine antagonist inhibited the lung myeloperoxidase activity. No tested antagonist significantly altered the lung and pleural TNF alpha and IL-1 beta production. We provide interesting evidence on the anti-inflammatory in vivo effects of non-peptide B-1 receptor antagonists. (c) 2006 Elsevier Inc. All rights reserved.