Pyrimethamine

Pyrimethamine is an antiparasitic drug that inhibits dihydrofolate reductase, disrupting folate metabolism in protozoa. It is used in combination regimens for malaria and toxoplasmosis.

Dihydrofolate reductase: An enzyme that reduces dihydrofolate to tetrahydrofolate, supplying folate cofactors for nucleotide synthesis. Pyrimethamine inhibits the parasite form of this enzyme.
Toxoplasmosis: An infection caused by the protozoan parasite Toxoplasma gondii. Pyrimethamine is used with other drugs to treat severe or active toxoplasmosis.
Trimethoprim: An antibacterial drug that inhibits bacterial dihydrofolate reductase. It targets the same enzyme class but is used mainly against bacteria.
Antimicrobial resistance: The ability of microorganisms to survive exposure to drugs that once inhibited or killed them. Resistance mutations can reduce parasite susceptibility to pyrimethamine.
Folate: A family of water-soluble B vitamins that supplies one-carbon units for making nucleotides and other molecules. Blocking folate recycling deprives susceptible parasites of materials needed for DNA synthesis.
Malaria: A mosquito-borne disease caused by Plasmodium parasites that infect the liver and red blood cells. Pyrimethamine has been used against malaria, usually in combination regimens.
Methotrexate: An antifolate drug used in cancer and immune-mediated disease that inhibits dihydrofolate reductase. It shares the enzyme target but has different clinical uses and toxicity considerations.
Plasmodium falciparum: A Plasmodium species that causes the most severe form of human malaria. Mutations in its dihydrofolate reductase can confer pyrimethamine resistance.
Sulfonamide: A class of drugs that inhibits enzymes in folate synthesis, including dihydropteroate synthase. Sulfonamides block a different step in the pathway and are paired with pyrimethamine in some regimens.
Sulfadiazine: A sulfonamide antibiotic that inhibits bacterial and protozoal folate synthesis. It is a standard partner for pyrimethamine in toxoplasmosis treatment.

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