Molecular action of methotrexate in inflammatory diseases.
Despite the recent introduction of biological response modifiers and potent new small-molecule antirheumatic drugs, the efficacy of methotrexate is nearly unsurpassed in the treatment of inflammatory arthritis. Although methotrexate was first introduced as an antiproliferative agent that inhibits the synthesis of purines and pyrimidines for the therapy of malignancies, it is now clear that many of the anti-inflammatory effects of methotrexate are mediated by adenosine. This nucleoside, acting at one or more of its receptors, is a potent endogenous anti-inflammatory mediator. In confirmation of this mechanism of action, recent studies in both animals and patients suggest that adenosine-receptor antagonists, among which is caffeine, reverse or prevent the anti-inflammatory effects of methotrexate.
Chan
Edwin S L
ES
Division of Clinical Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
Cronstein
Bruce N
BN
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use*; D018047:Receptors, Purinergic P1 / Q000378:metabolism
D018501:Antirheumatic Agents; D018047:Receptors, Purinergic P1; D000241:Adenosine; D008727:Methotrexate