title: Can we teach an old drug new tricks?
abstract: Although resistance to chloroquine (CQ) has relegated it from modern chemotherapeutic strategies to treat Plasmodium falciparum malaria, new evidence suggests that higher doses of the drug may exert a different killing mechanism and offers this drug a new lease of life. Whereas the established antimalarial mechanisms of CQ are usually associated with nanomolar levels of the drug, micromolar levels of CQ trigger a distinct cell death pathway involving the permeabilization of the digestive vacuole of the parasite and a release of hydrolytic enzymes. In this paper, we propose that this pathway is a promising antimalarial strategy and suggest that revising the CQ treatment regimen may elevate blood drug levels to trigger this pathway without increasing the incidence of adverse reactions.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. chngjunhong@hotmail.com
authors.forename: Jun-Hong
authors.initials: JH
authors.lastname: Ch'ng
authors.forename: Laurent
authors.initials: L
authors.lastname: Renia
authors.forename: Francois
authors.initials: F
authors.lastname: Nosten
authors.forename: Kevin S W
authors.initials: KS
authors.lastname: Tan
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000494:pharmacology*; D002738:Chloroquine / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D002738:Chloroquine