Abstract
Aromatic diamidines are potent trypanocides. Pentamidine, a diamidine, has been used for more than 60 years to treat human African trypanosomiasis (HAT); however, the drug must be administered parenterally and is active against first-stage HAT only, prior to the parasites causing neurological deterioration through invasion of the CNS. A major research effort to design novel diamidines has led to the development of orally active prodrugs and, remarkably, a new generation of compounds that can penetrate the CNS. In this review, progress in the development of diamidines for the treatment of HAT is discussed.
MeSH terms
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Animals
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Benzamidines / administration & dosage
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Benzamidines / pharmacokinetics
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Benzamidines / pharmacology*
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Benzamidines / therapeutic use*
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Biotransformation
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Brain / metabolism
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Clinical Trials as Topic
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Drug Design
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Drug Resistance
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Humans
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Pentamidine / administration & dosage
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Pentamidine / pharmacokinetics
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Pentamidine / pharmacology
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Pentamidine / therapeutic use*
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Prodrugs / administration & dosage
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Prodrugs / pharmacokinetics
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Prodrugs / pharmacology
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Prodrugs / therapeutic use
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Trypanocidal Agents / administration & dosage
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Trypanocidal Agents / pharmacokinetics
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Trypanocidal Agents / pharmacology
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Trypanocidal Agents / therapeutic use*
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Trypanosoma brucei gambiense / drug effects
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Trypanosoma brucei rhodesiense / drug effects
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Trypanosomiasis, African / drug therapy*
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Trypanosomiasis, African / parasitology
Substances
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Benzamidines
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Prodrugs
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Trypanocidal Agents
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Pentamidine
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pafuramidine