Smith S R, Watnick A W, Bryant R W, Billah M, Siegel M I
Schering-Plough Research Institute, Bloomfield, New Jersey.
J Pharmacol Exp Ther. 1992 Aug;262(2):721-8.
Sch 40120 (10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b] [1,8]naphthyridin-5(7H)-one) is an inhibitor of the 5-lipoxygenase enzyme in rat neutrophils, human neutrophils and the the MC9 murine mast cell clone with IC50 values of 8, 4 and 7 microM, respectively. The drug was examined for its effects on acute inflammatory responses in the paw and pleural cavity of rats. The drug suppressed paw inflammation triggered by a reverse passive Arthus reaction or a subplantar injection of the polysaccharide carrageenan with p.o. ED50 values of 0.2 and 1.5 mg/kg, respectively. In reverse passive Arthus reaction and carrageenan pleurisy models, Sch 40120 was found to suppress both the cellular and fluid components of the acute inflammation. The p.o. ED50 values for inhibition of cells and fluid in pleurisy models were in the range of 0.1 to 0.7 mg/kg. When applied locally to the ears of mice, the drug blocked an arachidonic acid-induced and leukotriene-mediated ear inflammation with an ED50 of 0.072 mg/ear. These findings suggest that Sch 40120 is a potent anti-inflammatory agent that may be particularly useful in the treatment of inflammatory diseases such as psoriasis in which leukotrienes appear to be major mediators of the pathological symptoms that characterize the disease state.
Sch 40120（10 -（3 - 氯苯基）- 6,8,9,10 - 四氢苯并[b][1,8]萘啶 - 5(7H)-酮）是一种5 - 脂氧合酶抑制剂，对大鼠中性粒细胞、人中性粒细胞及MC9小鼠肥大细胞克隆均有抑制作用，其IC50值分别为8、4和7微摩尔。研究了该药物对大鼠爪部和胸腔急性炎症反应的影响。该药物抑制由反向被动Arthus反应或足底注射多糖角叉菜胶引发的爪部炎症，口服给药的ED50值分别为0.2和1.5毫克/千克。在反向被动Arthus反应和角叉菜胶性胸膜炎模型中，发现Sch 40120可抑制急性炎症的细胞和液体成分。在胸膜炎模型中，抑制细胞和液体的口服ED50值在0.1至0.7毫克/千克范围内。当局部应用于小鼠耳部时，该药物可阻断花生四烯酸诱导的、白三烯介导的耳部炎症，ED50为0.072毫克/耳。这些发现表明，Sch 40120是一种强效抗炎药，可能对治疗银屑病等炎症性疾病特别有用，在银屑病中白三烯似乎是表征疾病状态的病理症状的主要介质。
