Accumulation of granulocytes in the lung and skin of guinea pigs. Inhibition by the anti-H1 antiallergic agent epinastine.

The aim of this study was to investigate whether the antiallergic/H1-antagonistic drug epinastine (WAL 801, Alesion, CAS 108929-04-0) inhibited inflammatory granulocyte infiltration in respiratory or dermal tissue. A late-phase bronchial eosinophilia was induced in sensitized and challenged guinea pigs, and a skin chamber technique was developed for assessing leukotriene-B4 (LTB4) induced transdermal chemotaxis in vivo in this species. Oral epinastine as well as the reference compounds beta-methasone and the LTB4-receptor antagonist 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy) propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid (ADCA) demonstrated a dose-dependent inhibition of granulocyte accumulation. The rank order of oral activity was epinastine > betamethasone > ADCA for bronchial eosinophilia and betamethasone > epinastine = ADCA for transdermal chemotaxis. These animal studies suggest a non-antihistamine activity of epinastine which may contribute to its clinical efficacy as an antiallergic drug.