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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 drug-resistant 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.<\/jats:p>","DOI":"10.1128\/aac.02582-16","type":"journal-article","created":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T20:40:36Z","timestamp":1488832836000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":313,"title":["Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance"],"prefix":"10.1128","volume":"61","author":[{"given":"Nuno","family":"Vale","sequence":"first","affiliation":[{"name":"UCIBIO\/REQUIMTE, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Porto, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Gouveia","sequence":"additional","affiliation":[{"name":"UCIBIO\/REQUIMTE, Chemistry and Biochemistry Department, Faculty of Sciences, University of Porto, Porto, Portugal"},{"name":"Center for the Study of Animal Science, ICETA, Porto, University of Porto, Portugal"},{"name":"ICBAS\u2014University of Porto, Porto, Portugal"}]},{"given":"Gabriel","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology &amp; Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine &amp; Health Sciences, George Washington University, Washington, DC, USA"}]},{"given":"Paul J.","family":"Brindley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology &amp; Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine &amp; Health Sciences, George Washington University, Washington, DC, USA"}]},{"given":"F\u00e1tima","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"ICBAS\u2014University of Porto, Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Porto, Portugal"}]},{"given":"Jos\u00e9 M.","family":"Correia da Costa","sequence":"additional","affiliation":[{"name":"Center for the Study of Animal Science, ICETA, Porto, University of Porto, Portugal"},{"name":"INSA-National Health Institute Dr. Ricardo Jorge, Porto, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"2","volume-title":"Prevention and control of schistosomiasis and soil-transmitted helminthiasis: report of a WHO expert committee: technical report series 912","author":"World Health Organization","year":"2002","unstructured":"World Health Organization. 2002. 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