Document Type
Journal Article
Publication Date
1-17-2018
Journal
Scientific Reports
Volume
8
Issue
1
Inclusive Pages
975
DOI
10.1038/s41598-017-18457-w
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 front-line drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Weeks, J., Roberts, W., Leasure, C., Suzuki, B., Robinson, K., Hawdon, J., & +several additional authors (2018). Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing.. Scientific Reports, 8 (1). http://dx.doi.org/10.1038/s41598-017-18457-w
Peer Reviewed
1
Open Access
1
Included in
Medical Immunology Commons, Medical Microbiology Commons, Parasitic Diseases Commons, Parasitology Commons, Tropical Medicine Commons
Comments
Reproduced with permission of Nature Journals. Scientific Reports