Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story.

Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story.
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DOI:
10.1016/j.pt.2012.12.005
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发表时间:
2013-03
影响因子:
9.6
通讯作者:
Horn D
Horn D
中科院分区:
医学1区
文献类型:
--
作者:
Baker N;de Koning HP;Mäser P;Horn D

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美拉胂醇和喷他脒是两大类主要药物,即砷类药物和二胺类药物,历史上用于治疗非洲锥虫引起的疾病:人类昏睡病和牲畜昏睡病。对这些药物的交叉耐药是在60多年前首次观察到的,目前仍是昏睡病治疗中交叉耐药的唯一例子。布鲁氏锥虫腺苷转运蛋白在两种药物摄取中的作用是众所周知的。最近,aquaglyceroporin 2 (AQP2)功能丧失与美拉索prol-pentamidine交叉耐药有关。AQP2似乎是一个促进药物积累的通道,也可能与临床耐药病例有关。在这里,我们回顾了这些发现,并考虑了一些新的问题以及未来的前景,以解决由这些寄生虫引起的毁灭性疾病。
Melarsoprol and pentamidine represent the two main classes of drugs, the arsenicals and diamidines, historically used to treat the diseases caused by African trypanosomes: sleeping sickness in humans and Nagana in livestock. Cross-resistance to these drugs was first observed over sixty years ago and remains the only example of cross-resistance among sleeping sickness therapies. A Trypanosoma brucei adenosine transporter is well-known for its role in the uptake of both drugs. More recently, aquaglyceroporin 2 (AQP2) loss-of-function was linked to melarsoprol-pentamidine cross-resistance. AQP2, a channel that appears to facilitate drug accumulation, may also be linked to clinical cases of resistance. Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites.
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