Praziquantel for schistosomiasis: Single-drug metabolism revisited, mode of action, and resistance

Nuno Vale*, Maria João Gouveia, Gabriel Rinaldi, Paul J. Brindley, Fátima Gärtner, José M.Correia Da Costa

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

227 Citations (SciVal)

Abstract

Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drugresistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.

Original languageEnglish
Article numbere02582
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number5
DOIs
Publication statusPublished - May 2017
Externally publishedYes

Keywords

  • Cytochromes P450
  • Enantiomers
  • Metabolism
  • Praziquantel
  • Schistosomiasis
  • Schistosoma/drug effects
  • Humans
  • Schistosomiasis/drug therapy
  • Africa South of the Sahara
  • Praziquantel/analogs & derivatives
  • Animals
  • Drug Resistance
  • Schistosomicides/metabolism

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