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Efflux of Chloroquine from Plasmodium falciparum : Mechanism of Chloroquine Resistance
Abstract
Chloroquine-resistant Plasmodium falciparum accumulate significantly less chloroquine than susceptible parasites, and this is thought to be the basis of their resistance. However, the reason for the lower accumulation of chloroquine was unknown. The resistant parasite has now been found to release chloroquine 40 to 50 times more rapidly than the susceptible parasite, although their initial rates of chloroquine accumulation are the same. Verapamil and two other calcium channel blockers, as well as vinblastine and daunomycin, each slowed the release and increased the accumulation of chloroquine by resistant (but not susceptible) Plasmodium falciparum . These results suggest that a higher rate of chloroquine release explains the lower chloroquine accumulation, and thus the resistance observed in resistant Plasmodium falciparum .
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Citations
Cited by
Contribution of the pfmdr1 gene to antimalarial drug-resistance
Duraisingh, M. T., & Cowman, A. F. (2005) · Acta Tropica · doi:10.1016/j.actatropica.2005.04.008 · Cited by 300
Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase.
Francis, S. E., Gluzman, I. Y., Oksman, A., Knickerbocker, A., Mueller, R., Bryant, M. L., Sherman, D. R., Russell, D. G., & Goldberg, D. E. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06263.x · Cited by 277
Self-citationSCHWAB, A. E., BOAKYE, D. A., KYELEM, D., & PRICHARD, R. K. (2005) · The American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2005.73.234 · Cited by 163
The Plasmodium digestive Vacuole: Metabolic Headquarters and Choice Drug Target
Olliaro, P. L., & Goldberg, D. E. (1995) · Parasitology Today · doi:10.1016/0169-4758(95)80042-5 · Cited by 139
Recent advances in antimalarial drug development
Vangapandu, S., Jain, M., Kaur, K., Patil, P., Patel, S. R., & Jain, R. (2007) · Medicinal Research Reviews · doi:10.1002/med.20062 · Cited by 108
Metadata
- Authors
- Krogstad, D. J., Gluzman, I. Y., Kyle, D. E., Oduola, A. M. J., Martin, S. K., Milhous, W. K., & Schlesinger, P. H.
- Venue
- Science
- Published
- 1987-11-27
- Volume
- 238
- Issue
- 4831
- Pages
- 1283-1285
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1996808398
- Cited by
- 532
- References
- 0
- FWCI
- 26.21
- Type
- journal article
- Language
- en
- Open access
- closed
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- Krogstad, D. J., Gluzman, I. Y., Kyle, D. E., Oduola, A. M. J., Martin, S. K., Milhous, W. K., & Schlesinger, P. H. (1987). Efflux of Chloroquine from Plasmodium falciparum : Mechanism of Chloroquine Resistance. Science. https://doi.org/10.1126/science.3317830
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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