期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1981
卷号：78
期号：4
页码：2053-2056
DOI：10.1073/pnas.78.4.2053
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Evidence is presented to show that nonsteroidal antiinflammatory drugs react with two sites on the cyclooxygenase (8,11,14-eicosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1 ). Although the degree of interaction with the catalytic site determines the potency of such compounds, interaction with the supplementary site is also obligatory for efficacy as cyclooxygenase inhibitors and may explain the selectivity of such drugs in inhibiting the cyclooxygenase but not the lipoxygenase pathway. Drugs that interact more effectively with the supplementary site than with the catalytic site--i.e., those of weak to moderate activity as cyclooxygenase inhibitors--are shown to prevent inhibition of the enzyme by indomethacin. Compounds in this class are also capable of blocking the ulcerogenic action of indomethacin, which suggests that this antiulcerogenic property stems from a direct action at the level of the cyclooxygenase in the stomach.
