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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.

Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing