Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Antifolates act specifically during DNA and RNA synthesis, exerting a cytotoxic effect during the S- phase of the cell cycle. The majority of antifolates work by inhibiting dihydrofolate reductase (DHFR). Meanwhile, immunosuppressive drugs are drugs that inhibit or prevent the activity of the immune system. Immunosuppressive drugs can be classified into five groups: glucocorticoids, cytostatics, antibodies, drugs acting on immunophilins and other drugs.

Methotrexate (also known as Amethopterin, CL14377 or WR19039), an antimetabolite and antifolate agent, is an immunosuppressant and antineoplastic agent.

Methotrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the conversion of folic acid into tetrahydrofolate, and inhibiting purine and pyrimidine synthesis. In addition, Methotrexate has the potential for the research of autoimmune diseases and a number of different cancers. Methotrexate is effective in RA as it interferes with the production of potent pro-inflammatory agents such as prostaglandins. Furthermore, Methotrexate has also been used as an adjunct therapy for persistent mild cardiac allograft rejection. Moreover, types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis (RA), and Crohn’s disease. Besides, Methotrexate selectively induces apoptosis of activated, but not resting lymphocytes, even after short-term exposure to Methotrexate and subsequent activation in drug-free medium.

To sum up, Methotrexate, an antimetabolite and antifolate agent, is an potent immunosuppressant and antineoplastic agent.

[1] David Banji, et al. Indian J Pharmacol. 2011 Sep;43(5):546-50.
[2] L Genestier, et al. 2000 May;47(2-3):247-57.