[{"id":27,"title":"Repurposing antipsychotic and sleep disorder drugs as anti-parasitics","sha":"60ce1d1ca8e506beecdcbbf186d38766","user_id":51,"state":"published","body":"Antipsychotic and sleep disorder drugs represent a rapidly growing, global market [(1)](http://www.ncbi.nlm.nih.gov/pubmed/21476952).  Novel drugs targeting melatonin [(2)](http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+20577266), serotonin [(3)](http://www.ncbi.nlm.nih.gov/pubmed/23757185), dopamine [(4)](http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+19909227), and GABA [(5)](http://www.ncbi.nlm.nih.gov/pubmed/24357084) receptors are being developed.  Historically, related compounds have been identified as demonstrating activity against flatworms and the model nematode _Caenorhabditis elegans_, but nothing has been done to reconcile the recent growing diversity of chemical derivatives with potential activity against parasitic worms [(6)](http://www.ncbi.nlm.nih.gov/pubmed/25516827).\r\n\r\nMelatonin is a well-known regulator of circadian rhythms in mammals, and Prazosin, an agonist of the mammalian melatonin 3 receptor, triggers various defects in _C. elegans_ [(7)](http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+17573073).  Melatonin has also been shown to promote protective effects in mice infected with _Schistosoma mansoni_ [(8)](http://www.ncbi.nlm.nih.gov/pubmed/11841922).\r\n\r\nIvermectin is a potent anti-parasitic which agonizes GABA receptors, causing flaccid paralysis and parasite death.  Benzodiazepine and non-benzodiazepine GABA receptor agonists could therefore prove effective anthelmintics.  Ivermectin exposure has also been found to enhance binding of certain benzodiazepine-derivatives in rats [(9)]( http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+6319606) providing some rationale for exploring combinatorial therapies.  Benzodiazepine derivatives have historically proven effective as anti-schistosomals [(10)]( http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+714190), providing further evidence of anti-parasitic efficacy within the family.\r\n\r\nSerotonin impacts motility and carbohydrate metabolism in flatworms [(11)]( http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+156397), and nematodes [(12)]( http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+6805073).  Dopamine impacts various behaviours in nematodes [(13)]( http://www.wormbook.org/chapters/www_monoamines/monoamines.html), and reduces motility in flatworms [(14)]( http://www.ncbi.nlm.nih.gov/pubmed/?term=Ribeiro+et+al.+(2005)+Parasitology+131%3A+S19-40).\r\n","created_at":"2015-02-12T13:46:24.474Z","updated_at":"2019-11-20T09:39:50.363Z","zenodo_id":22093,"doi":"http://dx.doi.org/10.5281/zenodo.15066","subject":null,"tags":["nematode","flatworm","sleep","serotonin","gaba","melatonin","dopamine","parasite","drugs","antipsychotic","anthelmintic"],"vote_count":11,"view_count":1,"score":11.1,"deleted":false,"muted":false,"tweeted":false,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null}]