title: Effects of dipyridamole on Plasmodium falciparum-infected erythrocytes.
abstract: This study assessed the antimalarial activity of dipyridamole, a well-known vasodilator and inhibitor of platelet aggregation. Dipyridamole was effective against all of the erythrocytic stages such as rings, trophozoites and schizonts, and induced ultrastructural changes during the transition from trophozoite to schizont in vitro. Merozoites were also inhibited from invading dipyridamole-treated erythrocytes. It seems that dipyridamole binds to the erythrocyte membrane blocking the receptors for the merozoite. The 50% inhibitory concentration (IC(50)) of dipyridamole against Plasmodium falciparum infection was 30 nM. The IC(50) of chloroquine decreased from 97.0 nM to 13.7 nM when combined with dipyridamole (0.1 nM). Therefore, we suggest that dipyridamole has antiplasmodial activity due to its ability to arrest parasite development and by inhibiting merozoite invasion of the erythrocytes. Chloroquine activity against P. falciparum is also enhanced by the addition of dipyridamole. Treatment with a combination of chloroquine and dipyridamole may lead to a more effective treatment for chloroquine-resistant strains of P. falciparum.
authors.affiliation: Research Institute of Science and Technology, Tokai University, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Akaki
authors.forename: Yamaji
authors.initials: Y
authors.lastname: Nakano
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Eiji
authors.initials: E
authors.lastname: Nagayasu
authors.forename: Masamichi
authors.initials: M
authors.lastname: Aikawa
mesh_terms: D000747:Anemia, Hypochromic; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000378:metabolism / Q000494:pharmacology; D004176:Dipyridamole / Q000819:agonists / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000469:parasitology*; D008018:Life Cycle Stages / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D013997:Time Factors
chemical_list: D000962:Antimalarials; D004176:Dipyridamole; D002738:Chloroquine