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., and Liachko, Nicole F. (2018) Sertraline, paroxetine, and chlorpromazine are rapidly acting anthelmintic drugs capable of clinical repurposing. Scientific Reports, 8.

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Abstract

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 frontline drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance.

Item ID:	52940
Item Type:	Article (Research - C1)
ISSN:	2045-2322
Additional Information:	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/.
Funders:	Department of Veterans Affairs (DVA), National Institute of Health (NIH), USA, University of Oregon, National Health and Medical Research Council (NHMRC), Australian Institute of Tropical Health and Medicine (AITHM), Swiss National Science Foundation (SNSF)
Projects and Grants:	DVA 1147891, DVA I01BX007080, NIH R01NS064131, NIH R01AI101369, NIH R21AI115012, NIH R01AI089896, NIH R01AI101369, NHMRC APP1091011, AITHM Capacity Building Grant 2016-17, SNSF P2ZHP3_161693, NHMRC APP1037304, NHMRC APP1020114
Date Deposited:	13 Apr 2018 02:04
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3214 Pharmacology and pharmaceutical sciences > 321402 Clinical pharmacology and therapeutics @ 100%
SEO Codes:	97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50% 92 HEALTH > 9299 Other Health > 929999 Health not elsewhere classified @ 50%
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