<unk>  interferes with the regeneration of tetrahydrofolic acid from dihydrofolate by competitively inhibiting the enzyme dihydrofolate reductase. Tetrahydrofolic acid is essential for DNA and RNA synthesis in many<unk> ecies, including protozoa. It has also been found to reduce the expression of SOD1, a key protein involved in amyotrophic lateral sclerosis. Other medications<unk>  is typically given with folinic acid and sulfadiazine. * Sulfonamides (e.g. sulfadiazine) inhibit dihydropteroate synthetase, an enzyme that participates in folic acid synthesis from para-aminobenzoic acid. Hence, sulfonamides work synergistically with<unk>  by blocking a different enzyme needed for folic acid synthesis. * Folinic acid (leucovorin) is a folic acid derivative converted to tetrahydrofolate, the primary active form of folic acid, in vivo, without relying on dihydrofolate reductase. Folinic acid reduces side effects related to folate deficiency in the patient. Mechanism of resistance Resistance to<unk>  is widespread. Mutations in the malarial gene for dihydrofolate reductase may reduce its effectiveness. These mutations decrease the binding affinity between<unk>  and dihydrofolate reductase via loss of hydrogen bonds and steric interactions.
Pyrimethamine
Quinine
Artemether
Phenpromethamine
Primaquine
Chloroquine
Mefloquine
Dimetacrine