Inhibition of the Presumably Leukotriene-Dependent Component of Antigen-Induced Bronchoconstriction in the Guinea Pig by Piriprost (U-60,257)

Abstract

Piriprost (U-60,257), a selective inhibitor of the 5-lipoxygenase, inhibited bronchoconstriction in a modification of the Konzett-Rossler procedure in which bronchoconstriction in sensitized guinea pigs may reflect leukotriene production. The duration of action of this compound and also the possible development of tachyphylaxis to its action upon repeated dosing were studied using a newly developed procedure for dosing conscious animals via the aerosol route. Duration of action with the lowest concentration which afforded maximum protection (180 s exposure to a 0.01% solution) was approximately 1.5 h. No decrease in drug potency was observed after 7 daily drug treatments.