[{"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},{"id":223,"title":"A proposal to search for patterns of genome changes across parasites","sha":"b7bdcee2f1c873432ec2709e937f15ac","user_id":null,"state":"published","body":"Parasites have co-evolved along with their hosts to utilise the host machinery to complete parts of the parasite’s life cycle. Despite potentially large implications for disease biology, common denominators for gene loss and gene gain have not been studied for human and important zoonotic parasites. Given the complete sequencing and good annotation of several parasitic genomes, we posit that identification of such common motifs would now be feasible. We expect different patterns in ectoparasites versus endoparasites, and extracellular versus intracellular parasites. There might be common motifs to genetic gains and losses in the host but we suspect that they would be harder to find than the common denominators in parasites.\r\n","created_at":"2015-09-16T13:19:43.088Z","updated_at":"2015-09-16T19:27:46.015Z","zenodo_id":61199,"doi":"http://dx.doi.org/10.5281/zenodo.31042","subject":null,"tags":["parasite","host","co-evolution","gene-loss","gene-gain"],"vote_count":1,"view_count":1,"score":1.1,"deleted":false,"muted":false,"tweeted":false,"attachment_file_name":null,"attachment_content_type":null,"attachment_file_size":null,"attachment_updated_at":null}]