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lüll Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis Tian H; Cronstein BNBull NYU Hosp Jt Dis 2007[]; 65 (3): 168-73Methotrexate has been widely used for the treatment of rheumatoid arthritis (RA). The mechanisms of action of methotrexate are complex. Developed as a folic acid analogue, methotrexate inhibits purine and pyrimidine synthesis, which accounts for its efficacy in the therapy of cancer as well as for some of its toxicities. Recently, many studies have focused on the adenosine-mediated antiinflammatory effects of methotrexate. Certain aspects of methotrexate toxicities are also attributed to adenosine release. A better understanding of the mechanisms of action and toxicities of methotrexate will direct clinicians in their treatment approach and toxicity monitoring. Toward that objective, the latest developments in the pharmacokinetics, mechanism of action, pharmacogenetics, and toxicity of methotrexate are herein discussed.|Adenosine/metabolism[MESH]|Antirheumatic Agents/adverse effects/pharmacokinetics/*pharmacology[MESH]|Arthritis, Rheumatoid/*drug therapy/genetics[MESH]|Drug Interactions[MESH]|Humans[MESH]|Methotrexate/adverse effects/pharmacokinetics/*pharmacology[MESH]|Pharmacogenetics[MESH] |