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]ethyl]-3-hydroxy-5-(3-pyridylmethoxy)-2-naphthamide), a new compound that inhibits both thromboxane A2 synthetase and 5-lipoxygenase and that functions 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 prevented the accumulation of eosinophils in the airways and this was paralleled by a decrease in the number of eosinophils and lymphocytes recovered in bronchoalveolar lavage fluid. F-1322 (0.1-10 microM) inhibited eotaxin-induced chemotaxis and actin polymerization of eosinophils in vitro in a concentration-dependent manner, while oral administration of F-1322 dose-dependently suppressed the migration of eosinophils into the airways in vivo in response to infusion of interleukin 5 and eotaxin in combination. F-1322 may, thus, improve the late asthmatic response in this model, in part, by preventing the accumulation of eosinophils in the airways. The pharmacological profile of F-1322 indicates that this drug is likely to be useful in the treatment of allergic diseases such as asthma.