Mechanism of Action of Methotrexate
Methotrexate is a chemotherapeutic agent and a disease-modifying antirheumatic drug (DMARD) primarily used to treat certain cancers and autoimmune diseases. The primary mechanism of action of methotrexate involves:
Inhibition of Dihydrofolate Reductase (DHFR): Methotrexate inhibits the enzyme dihydrofolate reductase, which is crucial for the reduction of dihydrofolate to tetrahydrofolate. This reaction is vital for the synthesis of purines and thymidylate, which are necessary precursors for DNA synthesis and cell division.
| Enzyme | Reaction Blocked |
|---|---|
| Dihydrofolate Reductase | Dihydrofolate to Tetrahydrofolate |
By inhibiting this enzyme, methotrexate disrupts DNA synthesis, thereby preventing rapidly dividing cells (such as cancer cells and activated immune cells in autoimmune diseases) from proliferating. This leads to cytotoxic effect, primarily on rapidly dividing cells, and an anti-inflammatory effect in autoimmune diseases.
While methotrexate affects several biochemical pathways due to its broad inhibition, the most significant impact is its action on DHFR, which is well-established as the primary mechanism by which methotrexate exerts its pharmacological effects.