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Science 20 February 1987:
Vol. 235. no. 4791, pp. 899 - 901
DOI: 10.1126/science.3544220
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Articles

Science, Vol 235, Issue 4791, 899-901
Copyright © 1987 by American Association for the Advancement of Science

articles

Reversal of chloroquine resistance in Plasmodium falciparum by verapamil

SK Martin, AM Oduola, and WK Milhous

The parasite Plasmodium falciparum, like neoplastic cells, develops resistance to multiple structurally unrelated drugs. If the mechanisms by which P. falciparum and neoplastic cells become resistant are similar, then it may be possible to reverse the resistance in the two types of cells by the same pharmacological agents. Verapamil, a calcium channel blocker, completely reversed chloroquine resistance in two chloroquine-resistant P. falciparum clones from Southeast Asia and Brazil. Verapamil reversed chloroquine resistance at the same concentration (1 X 10(-6)M) as that at which it reversed resistance in multidrug-resistant cultured neoplastic cells. This same concentration of verapamil had no effect on chloroquine-sensitive parasites. Hence, chloroquine resistance in P. falciparum may fit the criteria for the multidrug-resistant phenotype.


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Identification of a Chloroquine Importer in Plasmodium falciparum. DIFFERENCES IN IMPORT KINETICS ARE GENETICALLY LINKED WITH THE CHLOROQUINE-RESISTANT PHENOTYPE.
C. P. Sanchez, S. Wunsch, and M. Lanzer (1997)
J. Biol. Chem. 272, 2652-2658
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Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum.
C. Wilson, A. Serrano, A Wasley, M. Bogenschutz, A. Shankar, and D. Wirth (1989)
Science 244, 1184-1186
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Reversal of chloroquine resistance in malaria parasite Plasmodium falciparum by desipramine.
A. Bitonti, A Sjoerdsma, P. McCann, D. Kyle, A. Oduola, R. Rossan, W. Milhous, and D. Davidson Jr (1988)
Science 242, 1301-1303
   Abstract »    PDF »
Efflux of chloroquine from Plasmodium falciparum: mechanism of chloroquine resistance.
D. Krogstad, I. Gluzman, D. Kyle, A. Oduola, S. Martin, W. Milhous, and P. Schlesinger (1987)
Science 238, 1283-1285
   Abstract »    PDF »


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