Tsunoda H, Katayama S, Sakuma Y, Tanaka S, Tsukidate K, Abe S, Yamatsu I, Katayama K
Allergy and Asthma Research Unit, Eisai Co Ltd, Ibaraki, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1991 Jan;42(1):51-6. doi: 10.1016/0952-3278(91)90066-e.
6-Hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le 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-LTC4 and i-LTB4. These results suggest that E6080 may prove to be effective for the treatment of asthma, in which large amounts of leukotrienes (LTs) are elaborated.
6-羟基-2-(4-氨磺酰苄基氨基)-4,5,7-三甲基苯并噻唑盐酸盐（E6080）是一种口服活性且具有选择性的5-脂氧合酶抑制剂，它能剂量依赖性地抑制致敏清醒豚鼠吸入抗原（卵清蛋白）诱发的支气管痉挛。E6080的抑制作用比典型的5-脂氧合酶抑制剂AA861更强，但比白三烯（LT）拮抗剂LY171883弱。在被动致敏的豚鼠吸入抗原6小时后，检测支气管肺泡灌洗液（BALF）中的中性粒细胞和嗜酸性粒细胞浸润情况，E6080对中性粒细胞浸润的抑制作用比对嗜酸性粒细胞浸润的抑制作用更显著。通过观察肺组织显微照片证实了E6080对支气管肺泡细胞浸润和支气管上皮损伤的抑制作用。除上述药理作用外，E6080还能抑制BALF中i-LTC4和i-LTB4水平的升高。这些结果表明，E6080可能对治疗哮喘有效，因为哮喘患者体内会产生大量白三烯。
