{{Short description|Chemical compound}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 462260260 | image = Niclosamide.svg | image_class = skin-invert-image | image2 = Niclosamide-from-xtal-Mercury-3D-sf.png | image_class2 = bg-transparent
<!--Clinical data--> | tradename = Niclocide, Fenasal, Phenasal, others<ref name="pubchem">{{PubChem|4477}}</ref> | Drugs.com = {{drugs.com|CONS|niclosamide}} | pregnancy_category = | legal_status = | routes_of_administration = By mouth | ATC_prefix = P02 | ATC_suffix = DA01 | ATC_supplemental = {{ATCvet|P52|AG03}}
<!--Pharmacokinetic data--> | bioavailability = | metabolism = | elimination_half-life = | excretion =
<!--Identifiers--> | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 50-65-7 | PubChem = 4477 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB06803 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4322 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 8KK8CQ2K8G | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00436 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1448 | ChEBI = 7553
<!--Chemical data--> | IUPAC_name = 5-Chloro-''N''-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide | C=13 | H=8 | Cl=2 | N=2 | O=4 | smiles = Clc2cc(ccc2NC(=O)c1cc(Cl)ccc1O)[N+]([O-])=O | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C13H8Cl2N2O4/c14-7-1-4-12(18)9(5-7)13(19)16-11-3-2-8(17(20)21)6-10(11)15/h1-6,18H,(H,16,19) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = RJMUSRYZPJIFPJ-UHFFFAOYSA-N | melting_point = 225 | melting_high = 230 }} <!-- Definition and medical uses --> '''Niclosamide''', sold under the brand name '''Niclocide''' among others, is an anthelmintic medication used to treat tapeworm infestations, including diphyllobothriasis, hymenolepiasis, and taeniasis. It is not effective against other worms such as flukes or roundworms.<ref name=Cons2016>{{cite web|title=Niclosamide Advanced Patient Information - Drugs.com|url=https://www.drugs.com/cons/niclosamide.html|website=www.drugs.com|access-date=8 December 2016 |url-status=live |archive-url=https://web.archive.org/web/20161220223834/https://www.drugs.com/cons/niclosamide.html|archive-date=20 December 2016}}</ref> It is taken by mouth.<ref name=WHO2008>{{cite book | year = 2009 | veditors = Stuart MC, Kouimtzi M, Hill SR | title = WHO Model Formulary 2008 | publisher = World Health Organization | pages = 81, 87, 591 | isbn = 978-92-4-154765-9 | hdl = 10665/44053 | hdl-access = free }}</ref>
<!-- Side effects and mechanism --> Side effects include nausea, vomiting, abdominal pain, and itchiness. It may be used during pregnancy.<ref name=WHO2008/> It works by blocking glucose uptake and oxidative phosphorylation by the worm.<ref name=Riv2013>{{cite book | vauthors = Lanusse CE, Alvarez LI, Sallovitz JM, Mottier ML, Sanchez Bruni SF | date = 13 May 2013 | veditors = Riviere JE, Papich MG | chapter = Antinematodal Drugs | title = Veterinary Pharmacology and Therapeutics | publisher = John Wiley & Sons | page = 1096 | isbn = 978-1-118-68590-7 | archive-date = 10 September 2017 | archive-url = https://web.archive.org/web/20170910145626/https://books.google.com/books?id=xAPa4WDzAnQC&pg=PA1096 | chapter-url = https://books.google.com/books?id=xAPa4WDzAnQC&pg=PA1096 | url-status = live }}</ref>
<!-- Society and culture --> Niclosamide was first synthesized in 1958.<ref>{{cite book | vauthors = Mehlhorn H | date = 2008 | title = Encyclopedia of Parasitology: A-M | publisher = Springer Science & Business Media | page = 483 | isbn = 978-3-540-48994-8 | url = https://books.google.com/books?id=Jpg1ysgVn-AC&pg=PA483 | archive-date = 2016-12-20 | archive-url = https://web.archive.org/web/20161220080803/https://books.google.ca/books?id=Jpg1ysgVn-AC&pg=PA483 | url-status = live }}</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">{{cite book | year = 2019 | title = World Health Organization model list of essential medicines: 21st list 2019 | publisher = World Health Organization | hdl = 10665/325771 | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access = free | vauthors = Organization WH }}</ref> Niclosamide is not available for human use in the United States.<ref>{{cite web | url=https://www.cdc.gov/parasites/dipylidium/health_professionals/index.html | work = U.S. Centers for Disease Control and Prevention (CDC) | title = Dipylidium – Resources for Health Professionals | date=21 May 2020 }}</ref>
==Side effects== Side effects include nausea, vomiting, abdominal pain, constipation, and itchiness.<ref name=WHO2008/> Rarely, dizziness, skin rash, drowsiness, perianal itching, or an unpleasant taste occur. For some of these reasons, praziquantel is a preferable and equally effective treatment for tapeworm infestation.{{Citation needed|date = November 2015}}
Of note, niclosamide kills the pork tapeworm in a way that causes a multitude of viable eggs to be released and may result in cysticercosis. Neurocysticercosis is a life-threatening condition that may require brain surgery.<ref>{{cite book | date = 1980 | veditors = Remington JP, Osol A | title = Remington's Pharmaceutical Sciences | publisher = Mack Pub. Co. | edition = 16th | page = 1182 | location = Easton | oclc = 925174053 }}</ref><ref>{{cite book | date = 1982 | title = The Merck Manual of Diagnosis and Therapy | publisher = Merck Sharp & Dohme Research Laboratories | edition = 14th | page = 176 | isbn = 978-0-911910-03-2 | location = Rahway }}</ref>
==Mechanism of action== Niclosamide inhibits glucose uptake, oxidative phosphorylation, and anaerobic metabolism in the tapeworm.<ref name="pmid">{{cite journal | vauthors = Weinbach EC, Garbus J | title = Mechanism of action of reagents that uncouple oxidative phosphorylation | journal = Nature | volume = 221 | issue = 5185 | pages = 1016–1018 | date = March 1969 | pmid = 4180173 | doi = 10.1038/2211016a0 | s2cid = 4209497 | bibcode = 1969Natur.221.1016W }}</ref> It is a protonophore or proton shunt, disrupting proton gradients across membranes.<ref>{{cite journal | vauthors = Needham D | date = May 2024 | title = Niclosamide: A career builder | journal = Journal of Controlled Release | volume = 369 | pages = 786–856 | doi = 10.1016/j.jconrel.2023.07.016 | pmid = 37544514 }}</ref>
==Use as a pesticide== Niclosamide's metabolic effects are relevant to a wide ranges of organisms, and accordingly it has been applied as a control measure to organisms other than tapeworms. For example, it is an active ingredient in some formulations, such as Bayluscide, for killing lamprey larvae,<ref>{{cite book | vauthors = Boogaard MA | date = 2003 | chapter = Chapter 6: Delivery Systems of Piscicides | title = Integrated management techniques to control nonnative fishes. | publisher = US Geological Survey, Upper Midwest Environmental Sciences Center | pages = 39–50 | access-date = 2017-05-30 | archive-date = 2017-06-01 | archive-url = https://web.archive.org/web/20170601223345/https://www.usbr.gov/lc/phoenix/biology/azfish/pdf/borfinalreport6t7.pdf | location = La Crosse, Wisconsin | chapter-url = https://www.usbr.gov/lc/phoenix/biology/azfish/pdf/borfinalreport6t7.pdf }}</ref><ref>{{cite journal | vauthors = Dawson VK | date = 2003 | title = Environmental Fate and Effects of the Lampricide Bayluscide: a Review | journal = Journal of Great Lakes Research | volume = 29 | issue = Supplement 1 | pages = 475–492 | doi = 10.1016/S0380-1330(03)70509-7 | bibcode = 2003JGLR...29..475D }}</ref> as a molluscide,<ref name="whodat">{{Cite web | title = WHO Specifications And Evaluations. For Public Health Pesticides. Niclosamide | url = https://www.who.int/whopes/quality/en/Niclosamide.pdf | access-date = 2019-08-07 | archive-url = https://web.archive.org/web/20170110145622/http://www.who.int/whopes/quality/en/Niclosamide.pdf | archive-date = 2017-01-10 }}</ref> and as a general-purpose piscicide in aquaculture. Niclosamide has a short half-life in water in field conditions; this makes it valuable in ridding commercial fish ponds of unwanted fish; it loses its activity soon enough to permit restocking within a few days of eradicating the previous population.<ref name="whodat"/> Researchers have found that niclosamide is effective in killing invasive zebra mussels in cool freshwater aquatic environments.<ref>{{Cite news | vauthors = Blank L | date = 30 October 2018 |url=http://www.mndaily.com/article/2018/10/n-researchers-find-new-methods-to-combat-invasive-zebra-mussels|title=Researchers find new methods to combat invasive zebra mussels|work=The Minnesota Daily|access-date=2018-11-19|archive-date=2018-11-21|archive-url=https://web.archive.org/web/20181121072648/http://www.mndaily.com/article/2018/10/n-researchers-find-new-methods-to-combat-invasive-zebra-mussels}}</ref>
==Medical research== Niclosamide is under investigation as a potential treatment for certain types of cancer,<ref>{{cite web |title=Clinical Trials Using Niclosamide |url=https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/niclosamide |website=NCI |access-date=20 March 2019}}</ref> bacterial infections,<ref>{{cite journal | vauthors = Rajamuthiah R, Fuchs BB, Conery AL, Kim W, Jayamani E, Kwon B, Ausubel FM, Mylonakis E | title = Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus | journal = PLOS ONE | volume = 10 | issue = 4 | article-number = e0124595 | date = April 2015 | pmid = 25897961 | pmc = 4405337 | doi = 10.1371/journal.pone.0124595 | veditors = Planet PJ | bibcode = 2015PLoSO..1024595R | doi-access = free }}</ref> and viral infections.<ref>{{cite journal | vauthors = Li Y, Li P, He Q, Zhang R, Li Y, Kamar N, Peppelenbosch MP, de Man RA, Wang L, Pan Q | title = Niclosamide inhibits hepatitis E virus through suppression of NF-kappaB signalling | journal = Antiviral Research | volume = 197 | article-number = 105228 | date = January 2022 | pmid = 34929248 | doi = 10.1016/j.antiviral.2021.105228 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Braga L, Ali H, Secco I, Chiavacci E, Neves G, Goldhill D, Penn R, Jimenez-Guardeño JM, Ortega-Prieto AM, Bussani R, Cannatà A, Rizzari G, Collesi C, Schneider E, Arosio D, Shah AM, Barclay WS, Malim MH, Burrone J, Giacca M | title = Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia | journal = Nature | volume = 594 | issue = 7861 | pages = 88–93 | date = June 2021 | pmid = 33827113 | pmc = 7611055 | doi = 10.1038/s41586-021-03491-6 | bibcode = 2021Natur.594...88B }}</ref> It has been reported to localize to acidic cellular compartments, including tumor microenvironment and intracellular vesicles involved in viral replication.<ref>{{cite journal | vauthors = Jara MO, Williams III RO | date = 2023-03-01 | title = The challenge of repurposing niclosamide: Considering pharmacokinetic parameters, routes of administration, and drug metabolism | journal = Journal of Drug Delivery Science and Technology | volume = 81 | article-number = 104187 | doi = 10.1016/j.jddst.2023.104187 | issn = 1773-2247 }}</ref>
In 2018, niclosamide was observed to be a potent activator of PTEN-induced kinase 1 in primary cortical neurons.<ref>{{cite journal | vauthors = Barini E, Miccoli A, Tinarelli F, Mulholland K, Kadri H, Khanim F, Stojanovski L, Read KD, Burness K, Blow JJ, Mehellou Y, Muqit MM | title = The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1 | journal = ChemBioChem | volume = 19 | issue = 5 | pages = 425–429 | date = March 2018 | pmid = 29226533 | pmc = 5901409 | doi = 10.1002/cbic.201700500 }}</ref>
It appears to show ''in-vitro'' antifungal effects against some forms of eumycetoma.<ref>{{cite journal | vauthors = Mahmoud AB, Abd Algaffar S, van de Sande W, Khalid S, Kaiser M, Mäser P | title = Niclosamide Is Active In Vitro against Mycetoma Pathogens | journal = Molecules | volume = 26 | issue = 13 | page = 4005 | date = June 2021 | pmid = 34209118 | pmc = 8271592 | doi = 10.3390/molecules26134005 | doi-access = free }}</ref> {{clear}} == References == {{reflist}}
== Further reading == {{refbegin}} * {{cite book | vauthors = Taber CW, Venes D, Thomas CL | year = 2001 | title = Taber's Cyclopedic Medical Cictionary | publisher = F.A.Davis Co | edition = 19th | isbn = 978-0-8036-0655-5 | location = Philadelphia }} * {{cite book | year = 1995 | chapter = Helminths: Cestode (tapeworm) infection: Niclosamide | title = WHO model prescribing information: drugs used in parasitic diseases | publisher = World Health Organization (WHO) | edition = 2nd | isbn = 978-92-4-140104-3 | chapter-url = http://apps.who.int/medicinedocs/en/d/Jh2922e/3.1.3.html | hdl = 10665/41765 | hdl-access = free }} {{refend}}
== External links == * {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/niclosamide | archive-url = https://web.archive.org/web/20200922182900/https://druginfo.nlm.nih.gov/drugportal/name/niclosamide | archive-date = September 22, 2020 | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Niclosamide }} * {{PPDB|1929}} * {{cite web |url=https://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202406.html|title=MedlinePlus Drug Information: Niclosamide (Oral)|date=1995-06-23|website=MedlinePlus|publisher=U.S. National Library of Medicine|archive-url=https://web.archive.org/web/20061216072757/http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202406.html|archive-date=2006-12-16}}
{{portal bar|Medicine}} {{Anthelmintics}}
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