| RRC ID |
53953
|
| Author |
Weeks JC, Roberts WM, Leasure C, Suzuki BM, Robinson KJ, Currey H, Wangchuk P, Eichenberger RM, Saxton AD, Bird TD, Kraemer BC, Loukas A, Hawdon JM, Caffrey CR, Liachko NF.
|
| Title |
Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs Capable of Clinical Repurposing.
|
| Journal |
Sci Rep
|
| 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.
|
| Volume |
8(1)
|
| Pages |
975
|
| Published |
2018-1-17
|
| DOI |
10.1038/s41598-017-18457-w
|
| PII |
10.1038/s41598-017-18457-w
|
| PMID |
29343694
|
| PMC |
PMC5772060
|
| MeSH |
Ancylostoma / drug effects
Animals
Anthelmintics / pharmacology*
Caenorhabditis elegans / drug effects
Chlorpromazine / pharmacology*
Drug Discovery / methods
Drug Repositioning / methods
Drug Resistance / drug effects*
Paroxetine / pharmacology*
Schistosoma mansoni / drug effects
Sertraline / pharmacology*
|
| IF |
3.998
|
| Times Cited |
20
|
| Resource |
| C.elegans |
tm1325 |
