Plasmodium falciparum: in vitro drug interaction between chloroquine and enantiomers of amlodipine.
Both enantiomers of amlodipine, whose calcium antagonist action resides almost exclusively in the R(-) enantiomer, reversed chloroquine resistance in Plasmodium falciparum in vitro. R(-) enantiomer was slightly more effective than the S(+) enantiomer in potentiating chloroquine action against chloroquine-resistant strains of parasites. No potentiating effect was observed in chloroquine-sensitive parasites. Both enantiomers entered rapidly into parasitized erythrocytes to the same extent. Reversal of chloroquine resistance by the enantiomers of amlodipine was related to dose-dependent increase in the accumulation of chloroquine inside the erythrocytes parasitized by resistant parasites. These results suggest that the potentiating effect on chloroquine is independent of calcium metabolism of malaria parasites.
Basco
L K
LK
Centre National de Référence pour la Chimiosensibilité du Paludisme, Institut de Médecine et d'Epidémiologie Africaines et Tropicales, Hôpital Bichat-Claude Bernard, Paris, France.
Le Bras
J
J
D017311:Amlodipine; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D004357:Drug Synergism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D015394:Molecular Structure; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D017311:Amlodipine; D002738:Chloroquine; D009543:Nifedipine; D002118:Calcium