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Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing
Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. 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 Ca...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772060/ https://www.ncbi.nlm.nih.gov/pubmed/29343694 http://dx.doi.org/10.1038/s41598-017-18457-w |
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author | Weeks, Janis C. Roberts, William M. Leasure, Caitlyn Suzuki, Brian M. Robinson, Kristin J. Currey, Heather Wangchuk, Phurpa Eichenberger, Ramon M. Saxton, Aleen D. Bird, Thomas D. Kraemer, Brian C. Loukas, Alex Hawdon, John M. Caffrey, Conor R. Liachko, Nicole F. |
author_facet | Weeks, Janis C. Roberts, William M. Leasure, Caitlyn Suzuki, Brian M. Robinson, Kristin J. Currey, Heather Wangchuk, Phurpa Eichenberger, Ramon M. Saxton, Aleen D. Bird, Thomas D. Kraemer, Brian C. Loukas, Alex Hawdon, John M. Caffrey, Conor R. Liachko, Nicole F. |
author_sort | Weeks, Janis C. |
collection | PubMed |
description | Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. 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 Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching and development of Ancylostoma caninum hookworms and kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth species. C. elegans 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. |
format | Online Article Text |
id | pubmed-5772060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57720602018-01-26 Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing Weeks, Janis C. Roberts, William M. Leasure, Caitlyn Suzuki, Brian M. Robinson, Kristin J. Currey, Heather Wangchuk, Phurpa Eichenberger, Ramon M. Saxton, Aleen D. Bird, Thomas D. Kraemer, Brian C. Loukas, Alex Hawdon, John M. Caffrey, Conor R. Liachko, Nicole F. Sci Rep Article Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. 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 Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching and development of Ancylostoma caninum hookworms and kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth species. C. elegans 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. Nature Publishing Group UK 2018-01-17 /pmc/articles/PMC5772060/ /pubmed/29343694 http://dx.doi.org/10.1038/s41598-017-18457-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Weeks, Janis C. Roberts, William M. Leasure, Caitlyn Suzuki, Brian M. Robinson, Kristin J. Currey, Heather Wangchuk, Phurpa Eichenberger, Ramon M. Saxton, Aleen D. Bird, Thomas D. Kraemer, Brian C. Loukas, Alex Hawdon, John M. Caffrey, Conor R. Liachko, Nicole F. Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing |
title | Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing |
title_full | Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing |
title_fullStr | Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing |
title_full_unstemmed | Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing |
title_short | Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing |
title_sort | sertraline, paroxetine, and chlorpromazine are rapidly acting anthelmintic drugs capable of clinical repurposing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772060/ https://www.ncbi.nlm.nih.gov/pubmed/29343694 http://dx.doi.org/10.1038/s41598-017-18457-w |
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