title: Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story.
abstract: 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.
authors: London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
authors: Nicola
authors: N
authors: Baker
authors: Harry P
authors: HP
authors: de Koning
authors: Pascal
authors: P
authors: Mäser
authors: David
authors: D
authors: Horn
mesh_terms: D000818:Animals; D051397:Aquaglyceroporins / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D008549:Melarsoprol / Q000627:therapeutic use*; D010419:Pentamidine / Q000627:therapeutic use*; D010802:Phylogeny; D014344:Trypanocidal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014346:Trypanosoma brucei brucei / Q000145:classification / Q000187:drug effects / Q000235:genetics; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D051397:Aquaglyceroporins; D014344:Trypanocidal Agents; D010419:Pentamidine; D008549:Melarsoprol
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