title: Primaquine synergises the activity of chloroquine against chloroquine-resistant P. falciparum.
abstract: In recent years, resistance to the antimalarial drug, chloroquine, has become widespread. It is, therefore, imperative to find compounds that could replace chloroquine or work synergistically with this drug to overcome chloroquine resistance. We have examined the interaction between chloroquine, a 4-aminoquinoline, and a number of 8-aminoquinolines, including primaquine, a drug that is widely used to treat Plasmodium vivax infections. We find that primaquine is a potent synergiser of the activity of chloroquine against chloroquine-resistant Plasmodium falciparum. Analysis of matched transfectants expressing mutant and wild-type alleles of the P. falciparum chloroquine resistance transporter (PfCRT) indicate that primaquine exerts its activity by blocking PfCRT, and thus enhancing chloroquine accumulation. Our data suggest that a novel formulation of two antimalarial drugs already licensed for use in humans could be used to treat chloroquine-resistant parasites.
authors.affiliation: Molecular and Biochemical Parasitology Group, Liverpool School of Tropical Medicine, UK.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Bray
authors.forename: Samantha
authors.initials: S
authors.lastname: Deed
authors.forename: Emma
authors.initials: E
authors.lastname: Fox
authors.forename: Martha
authors.initials: M
authors.lastname: Kalkanidis
authors.forename: Mathirut
authors.initials: M
authors.lastname: Mungthin
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Deady
authors.forename: Leann
authors.initials: L
authors.lastname: Tilley
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D009682:Magnetic Resonance Spectroscopy; D010963:Plasmodium falciparum / Q000187:drug effects*; D011319:Primaquine / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D011319:Primaquine