Methotrexate is best described as which type of agent?

• A. Folate antagonist
• B. COX inhibitor
• C. TNF inhibitor
• D. PDE inhibitor

Answer: (A)

Methotrexate works by blocking folate metabolism. It inhibits the enzyme dihydrofolate reductase, which is needed to regenerate tetrahydrofolate. Without tetrahydrofolate, cells can’t efficiently make thymidylate and purines, so DNA synthesis and cell replication slow down, especially in rapidly dividing immune cells. That’s why methotrexate is classified as a folate antagonist and used to dampen immune activity in inflammatory diseases. At low doses, it also has anti-inflammatory effects partly through increased adenosine, but the core action is inhibition of folate metabolism. The other options describe mechanisms of different drug classes (COX inhibitors, TNF inhibitors, PDE inhibitors) and do not reflect methotrexate’s action.