London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
Trends Parasitol. 2013 Mar;29(3):110-8. doi: 10.1016/j.pt.2012.12.005. Epub 2013 Jan 30.
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 60 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.
梅拉胂醇和戊烷脒代表了两类主要的药物，即砷剂和二脒类，历史上用于治疗由非洲锥虫引起的疾病：人类的昏睡病和家畜的那加那病。这些药物之间的交叉耐药性早在 60 多年前就首次被观察到，至今仍是昏睡病治疗中唯一的交叉耐药性例子。一种布鲁氏锥虫腺苷转运蛋白因其在两种药物的摄取中的作用而广为人知。最近，水甘油通道蛋白 2（AQP2）的功能丧失与梅拉胂醇-戊烷脒的交叉耐药性有关。AQP2 是一种似乎有助于药物积累的通道，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应对这些寄生虫引起的破坏性疾病的前景。
