Effect of a novel 5-lipoxygenase inhibitor, E6080 on bronchospasm, airway cellular infiltration and leukotriene production in guinea pigs

6-Hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazole hydrochloride (E6080), an orally active and selective 5-lipoxygenase inhibitor, dose-dependently inhibited the bronchospasm induced by antigen (ovalbumin) inhalation in sensitized conscious guinea pigs. The inhibitory effect of E6080 was more potent than that of a typical 5-lipoxygenase inhibitor, AA861, but less than that of a leukotriene (LT) antagonist, LY171883. When airway infiltration of neutrophils and eosinophils was measured in bronchoalveolar lavage fluid (BALF) at 6 h after antigen inhalation by passively sensitized guinea pigs, the inhibitory effect of E6080 on neutrophil infiltration was more marked than that on eosinophil infiltration. The inhibitory effect of E6080 on bronchoalveolar cellular infiltration and bronchoepithelial damage was confirmed by examination of photomicrographs of the lung. In addition to the above pharmacological effects, E6080 inhibited the increase in BALF levels of both i-LTC 4 and i-LTB 4. These results suggest that E6080 may prove to be effective for the treatment of asthma, in which large amounts of leukotrienes (LTs) are elaborated.