Reversal of chloroquine resistance in falciparum malaria by some calcium channel inhibitors and optical isomers is independent of calcium channel blockade.
Various types of calcium channel blockers verapamil, gallopamil, devapamil, diltiazem, and nifedipine and a calmodulin inhibitor R24571 were evaluated for reversal of chloroquine(CQ) resistance of Plasmodium falciparum in an in vitro system. The results demonstrated that some of the above Ca2+ antagonists such as verapamil, gallopamil, devapamil and diltiazem were found to exert remarkable reversal activity of CQ resistance of the falciparum parasite in vitro, while the others like nifedipine and R24571 had no reversal properties of CQ resistance of the parasite. In addition, reversal activities of the CQ resistance by enantiomers of some calcium channel blockers(R-(+)-verapamil, R-(+)-gallopamil and R-(+)-devapamil), which do not bind to the calcium channel, were also observed in this study. The data strongly indicate that the mechanism of reversal of CQ resistance of falciparum malaria in vitro is independent of the calcium channel.
Ye
Z
Z
Department of Pharmacology, China Academy of Traditional Chinese Medicine, Beijing.
Van Dyke
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D004347:Drug Interactions; D004351:Drug Resistance; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D002738:Chloroquine