Primaquine synergises the activity of chloroquine against chloroquine-resistant P. falciparum
- 作者：Patrick G. Bray ; Samantha Deed ; Emma Fox ; Martha Kalkanidis ; Mathirut Mungthin ; Leslie W. Deady and Leann Tilley
- 关键词：Malaria ; 8-Aminoquinoline ; Primaquine ; Chloroquine ; Drug resistance ; Resistance reversing agent
- 刊名：Biochemical Pharmacology
- 出版年：2005
- 期刊代码：2_00062952
- 类别：pha
- 出版时间：2005
- 卷：70
- 期：8
- 页码：1158-1166
- 文件大小：305 K
摘要
In recent years, resistance to the antimalarial drug, chloroquine, has become widespread. It is, therefore, imperative to find compounds that could replace chloroquine or work synergistically with this drug to overcome chloroquine resistance. We have examined the interaction between chloroquine, a 4-aminoquinoline, and a number of 8-aminoquinolines, including primaquine, a drug that is widely used to treat Plasmodium vivax infections. We find that primaquine is a potent synergiser of the activity of chloroquine against chloroquine-resistant Plasmodium falciparum. Analysis of matched transfectants expressing mutant and wild-type alleles of the P. falciparum chloroquine resistance transporter (PfCRT) indicate that primaquine exerts its activity by blocking PfCRT, and thus enhancing chloroquine accumulation. Our data suggest that a novel formulation of two antimalarial drugs already licensed for use in humans could be used to treat chloroquine-resistant parasites.