About Methotrexate Antimetabolite ,antifolate, Immunosuppressant, Antineoplastic, Antirheumatic. Mechanism of Action of Methotrexate Drug inhibits the enzyme dihydrofolate reductase (DHFR), which catalyses the conversion of dihydrofolate to active tetrahydrofolate.It is an important step in the folic acid synthesis. Folic acid is needed for the de novo nucleoside thymidine, required for DNA synthesis. Drug therefore, inhibit the synthesis of DNA, RNA and protein. In lower doses it inhibit the enzyme involved in purine metabolism, leading to accumulation of adenosine, or the inhibition of T-cell activation and suppression of intercellular adhesion molecule expression by T-cells. Indications for Methotrexate 1. Acute lymphoblastic leukemia 2. Choriocarcinoma 3. Burkitt`s lymphoma 4. Meningeal leukemia 5. Lymphosarcoma 6. Hydatidiform mole 7. Psoriasis 8. Rheumatoid arthritis 9. Corticosteroid dependant asthma 10. Non metastatic osteosarcoma 11. Mycosis fungoides