Folate synthesis inhibitors

Folate synthesis inhibitors

Folate synthesis inhibitors proguanil and pyrimethamine act similar in protozoa as trimethoprim in bacteria: they inhibit the enzyme dihydrofolate reductase. Without folic acid the parasite cannot synthesize nucleic acids.

Pyrimethamine is usually given in combination with a sulphonamide to enhance folate synthesis inhibition. This combination can treat malaria and toxoplasmosis.

Pyrimethamine has low toxicity when applied in low doses. Rash is a side effect; in high doses folate deficiency can occur, causing depression of haematopoiesis. In high doses it can have teratogenic effects.


A sulfonamide is combined with pyrimethamine to produce an antimalarial action by sequential blockade of folate synthesis in sensitive Plasmodium strains.


Co-treatment with proguanil and pyrimethamine is preferred since cross-resistance can easily develop when used separately.