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To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode <jats:italic>Caenorhabditis elegans<\/jats:italic>. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill <jats:italic>C. elegans<\/jats:italic> at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit <jats:italic>C. elegans<\/jats:italic> feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult <jats:italic>Trichuris muris<\/jats:italic> whipworms, prevent hatching and development of <jats:italic>Ancylostoma caninum<\/jats:italic> hookworms and kill <jats:italic>Schistosoma mansoni<\/jats:italic> flatworms, three widely divergent parasitic helminth species. <jats:italic>C. elegans<\/jats:italic> mutants with resistance to known anthelmintic drugs such as ivermectin are equally or more susceptible to these three drugs, suggesting that they may act on novel targets to kill worms. Sertraline, paroxetine, and chlorpromazine have long histories of use clinically as antidepressant or antipsychotic medicines. They may represent new classes of anthelmintic drug that could be used in combination with existing front-line drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance.<\/jats:p>","DOI":"10.1038\/s41598-017-18457-w","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T15:29:06Z","timestamp":1515684546000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing"],"prefix":"10.1038","volume":"8","author":[{"given":"Janis C.","family":"Weeks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn","family":"Leasure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin J.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Currey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phurpa","family":"Wangchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon M.","family":"Eichenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleen D.","family":"Saxton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Bird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Kraemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Hawdon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor R.","family":"Caffrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole F.","family":"Liachko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,17]]},"reference":[{"key":"18457_CR1","unstructured":"Report of the third global meeting of the partners for parasite control. 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