Methotrexate
Methotrexate (formerly Amethopterin) is an antimetabolite drug used in treatment of cancer and autoimmune disease. It acts by inhibiting the metabolism of folic acid.
Uses
Methotrexate was originally used to treat many kinds of cancers as a type of chemotherapy. It is still the mainstay for treatment of acute lymphoblastic leukemia.
More recently it has come into use as a treatment for some autoimmune diseases, including psoriasis and arthritis. In the case of rheumatoid arthritis, parallel use with infliximab or etanercept has been shown to markedly improve symptoms.
It can be taken orally or by injection. Although daily preparations are occasionally used, many patients take weekly doses, which decreases the risk of certain side-effects.
Adverse effects
Possible side effects can include anemia, neutropenia, increased risk of bruising, and nausea. A small percentage of patients develop hepatitis, while there is an increased risk of pulmonary fibrosis.
The higher doses of methotrexate often used in cancer chemotherapy can cause toxic effects to the rapidly-dividing cells of bone marrow and gastrointestinal mucosa. The resulting myelosuppression and mucositis are often prevented (termed methotrexate "rescue") by using folinic acid supplements (not to be confused with folic acid).
Chemistry
Methotrexate's empirical formula is C20H22N8O5. Its structural name is N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid.
Mode of action
Methotrexate inhibits dihydrofolate reductase, an enzyme that is part of the folic acid metabolism. As folic acid is important in DNA synthesis, rapidly dividing cells develop a relative shortage of folic acid and die.
