What is methotrexate and how does it work?

• A. A nonsteroidal anti-inflammatory drug that reduces inflammation.
• B. A monoclonal antibody targeting folate receptors.
• C. A chemotherapy agent that acts as a folate analogue inhibiting dihydrofolate reductase.
• D. A chemotherapy agent that acts as a folate analogue and competitively inhibits dihydrofolate reductase, impairing DNA synthesis.

Answer: (D)

Methotrexate works by acting as a folate analogue that competes with the natural substrate for the enzyme dihydrofolate reductase. By inhibiting DHFR, the cell’s pool of tetrahydrofolate drops, limiting the production of thymidylate and purines needed for DNA synthesis. With less building blocks available, rapidly dividing cells can’t replicate DNA efficiently, leading to reduced cell proliferation—this underpins its use as a chemotherapy agent and its effectiveness in some autoimmune conditions at lower doses. It’s not an NSAID and not a monoclonal antibody; those descriptions refer to different drug classes. The most precise description is that methotrexate competitively inhibits DHFR, impairing DNA synthesis.