What is Pyrimethamine used for?

Introduction

Pyrimethamine is an antimalarial drug with a 2,4-daminopyrimide derivative. 2,4-diamniopyrimides were powerful antagonists of pteroylglutamic acid, further suggesting that Pyrimethamine had anti-malarial activity. WHO declared Pyrimethamine as an essential medicine (satisfies the priority health care need of the population determined by WHO) as it was an effective drug for treating P.falciparum strains of malaria.

Uses

Pyrimethamine (Daraprim®) was discovered in 1952 and introduced to the market in 1953. It is a synthetic derivative of ethyl pyrimidine, belonging to the diaminopyrimidines and antimalarials. It is a folic acid antagonist, acting as a competitive inhibitor of dihydrofolate reductase (DHFR), thus blocking the biosynthesis of purines and pyrimidines. It is used to treat acute malaria and in combination with sulfonamides (sulfadoxine, Fansidar®, or sulfadiazine) or antibiotics (azithromycin, clindamycin) to treat toxoplasmosis and neosporosis. It was also used to treat cystoisosporiasis in humans. It may be used for the prevention of malaria in areas nonresistant to Pyrimethamine; however, in humans, resistance to Pyrimethamine is prevalent worldwide, so the drug alone is no longer recommended by the US Centers for Disease Control and Prevention or other experts for prevention of malaria.

Pyrimethamine is distributed mainly to the kidneys, liver, spleen, and lungs and is well absorbed from the gastrointestinal tract. It is contraindicated in individuals with impaired renal and hepatic functions, with megaloblastic anemia caused by folate deficiency, and in pregnant females.

Used in animals

In veterinary medicine, it has been successfully used to treat hepatozoonosis, leishmaniasis, neosporosis, sarcocystosis, and toxoplasmosis. The treatment of neosporosis in dogs has limited efficacy and does not entirely eliminate N. caninum from the body. For neurological signs of neosporosis, a combination of Pyrimethamine with sulfadiazine is the best treatment option because of its more efficient penetration into the CNS.

References

[1] Pyrimethamine - an overview | ScienceDirect Topics https://www.sciencedirect.com/topics/neuroscience/pyrimethamine

[2] Synthesis of Pyrimethamine - Issuu https://issuu.com/barkercollege/docs/2021_science_journal/s/13380581