How does Methotrexate exert its therapeutic effect?

Methotrexate exerts its therapeutic effect primarily by inhibiting dihydrofolate reductase. This enzyme plays a crucial role in the synthesis of folate and subsequently in the production of nucleotides. By inhibiting dihydrofolate reductase, Methotrexate effectively depletes the folate pool within cells, which is vital for DNA synthesis and cell replication. This mechanism is particularly important in rapidly dividing cells, such as those found in certain cancers and in autoimmune diseases, where the drug can help to slow down or inhibit unwanted cell proliferation.

The inhibition of dihydrofolate reductase is a well-established mechanism that underpins the use of Methotrexate in treating conditions like rheumatoid arthritis and neoplastic diseases. The decrease in folate availability leads to decreased synthesis of purines and thymidylate, inhibiting cellular growth and division. This is why Methotrexate is categorized as an antimetabolite.

Other potential mechanisms listed, such as inhibiting protein synthesis, affecting calcium channels, or stimulating adrenal output, are not how Methotrexate works therapeutically, reinforcing the importance of dihydrofolate reductase inhibition in its pharmacological action.