甲氨蝶呤作用机制V71S1.pdfVIP

Bulletin of the Hospital for Joint Diseases 2013;71(Suppl 1):S5-8 S5 Mechanisms of Action of Methotrexate Edwin S. L. Chan, M.D., and Bruce N. Cronstein, M.D. Abstract attributed to its ability to inhibit key enzymes in the bio- As one of the most utilized disease-modifying anti-rheumatic synthesis of purines and pyrimidines, thereby attenuating drugs, methotrexate (MTX) has revolutionized the treatment malignant cell proliferation and turnover. As a potent inhibi- of rheumatoid arthritis as well as many other non-rheumatic tor of dihydrofolate reductase, the rate-limiting enzyme in chronic inflammatory diseases. Far from a simple anti- the production of tetrahydrofolate, it decreases the de novo proliferative agent as was once thought, our understanding production of purines and pyrimidines and interferes with of how it exerts its anti-inflammatory effects has grown over DNA synthesis. It is, therefore, not surprising that it may find the years. The mechanisms of action of MTX are reviewed application in inflammatory diseases where a high turnover here, and we look at how this knowledge helps to explain of inflammatory cells, such as T lymphocytes, in target tis- some of its most common side effects. sues is rampant. The effectiveness of MTX in this regard is undisputed, but the inhibition of cellular turnover is also the ow widely regarded as a gold standard in the therapy culprit behind many of the side effects of MTX, such as bone of rheumatoid arthritis and many other inflammatory marrow suppression and stomatitis