Suppressive effects of F-1322 on the antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs

We investigated the effects of F-1322 (N-[2-[4-(benzhydryloxy)piperidino]et hyl]-3-hydroxy-5-(3-pyridylmethoxy)-2-naphthamide), a new compound that inh ibits both thromboxane A(2) synthetase and 5-lipoxygenase and that function s as a histamine antagonist, on the Ascaris antigen-induced late asthmatic response and pulmonary eosinophilia in guinea pigs. Oral administration of F-1322 (10-100 mg/kg) inhibited the antigen-induced late asthmatic response in a dose-dependent manner. Histological analysis revealed that F-1322 pre vented the accumulation of eosinophils in the airways and this was parallel ed by a decrease in the number of eosinophils and lymphocytes recovered in bronchoalveolar lavage fluid. F-1322 (0.1-10 muM) inhibited eotaxin-induced chemotaxis and actin polymerization of eosinophils in vitro in a concentra tion-dependent manner, while oral administration of F-1322 dose-dependently suppressed the migration of eosinophils into the airways in vivo in respon se to infusion of interleukin 5 and eotaxin in combination. F-1322 may, thu s, improve the late asthmatic response in this model, in part, by preventin g the accumulation of eosinophils in the airways. The pharmacological profi le of F-1322 indicates that this drug is likely to be useful in the treatme nt of allergic diseases such as asthma. (C) 2001 Elsevier Science B.V. All rights reserved.