Niclosamide

Niclosamide
Clinical data
Trade names	Niclocide, Fenasal, Phenasal, others
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Routes of; administration	By mouth
ATC code	P02DA01(WHO)QP52AG03(WHO);
Identifiers
	IUPAC name 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide;
CAS Number	50-65-7;
PubChemCID	4477;
DrugBank	DB06803;
ChemSpider	4322;
UNII	8KK8CQ2K8G;
KEGG	D00436;
ChEBI	CHEBI:7553;
ChEMBL	ChEMBL1448;
CompTox Dashboard(EPA)	DTXSID7040362;
ECHA InfoCard	100.000.052
Chemical and physical data
Formula	C13H8Cl2N2O4
Molar mass	327.12g·mol−1
3D model (JSmol)	Interactive image;
Melting point	225 to 230 °C (437 to 446 °F)
	SMILES Clc2cc(ccc2NC(=O)c1cc(Cl)ccc1O)[N+]([O-])=O;
	InChI InChI=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); Key:RJMUSRYZPJIFPJ-UHFFFAOYSA-N;
	(what is this?)(verify)

Niclosamide,sold under the brand nameNiclocideamong others, is ananthelminticmedication used to treattapeworminfestations, includingdiphyllobothriasis,hymenolepiasis,andtaeniasis.It is not effective against other worms such asflukesorroundworms.^[2]It is taken by mouth.^[3]

Side effects include nausea, vomiting, abdominal pain, and itchiness. It may be used during pregnancy.^[3]It works by blockingglucose uptakeandoxidative phosphorylationby the worm.^[4]

Niclosamide was first synthesized in 1958.^[5]It is on theWorld Health Organization's List of Essential Medicines.^[6]Niclosamide is not available for human use in the United States.^[7]

Side effects[edit]

Side effects include nausea, vomiting, abdominal pain,constipation,and itchiness.^[3]Rarely, dizziness, skin rash, drowsiness, perianal itching, or an unpleasant taste occur. For some of these reasons,praziquantelis a preferable and equally effective treatment for tapeworm infestation.^{[citation needed]} Important Note: Niclosamide kills the pork tapeworm and results in its digestion. This then may cause a multitude of viable eggs to be released and may result incysticercosis.Therefore, a purge should be given 1 or two hours after treatment. CNS cysticercosis is a life-threatening condition and may require brain surgery.^[8]^[9]

Mechanism of action[edit]

Niclosamide inhibitsglucoseuptake, oxidativephosphorylation,and anaerobic metabolism in the tapeworm.^[10]

Other applications[edit]

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 killinglampreylarvae,^[11]^[12]as a molluscide,^[13]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 re-stocking within a few days of eradicating the previous population.^[13]Researchers have found that niclosamide is effective in killing invasivezebra musselsin cool waters.^[14]

Research[edit]

Niclosamide is under investigation for applications against types of cancer,^[15]bacterial infections,^[16]or viral infections.^[17]^[18]

In 2018, niclosamide was observed to be a potent activator ofPTEN-induced kinase 1in primary cortical neurons.^[19]

References[edit]

^CID 4477fromPubChem
^"Niclosamide Advanced Patient Information - Drugs.com".www.drugs.com.Archivedfrom the original on 20 December 2016.Retrieved8 December2016.
^^a ^b ^cWorld Health Organization(2009). Stuart MC, Kouimtzi M, Hill SR (eds.).WHO Model Formulary 2008.World Health Organization. pp. 81, 87, 591.hdl:10665/44053.ISBN 9789241547659.
^Lanusse CE, Alvarez LI, Sallovitz JM, Mottier ML, Sanchez Bruni SF (13 May 2013)."Antinematodal Drugs".In Riviere JE, Papich MG (eds.).Veterinary Pharmacology and Therapeutics.John Wiley & Sons. p. 1096.ISBN 978-1-118-68590-7.Archivedfrom the original on 10 September 2017.
^Mehlhorn H (2008).Encyclopedia of Parasitology: A-M.Springer Science & Business Media. p. 483.ISBN 978-3-540-48994-8.Archivedfrom the original on 2016-12-20.
^World Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^"Dipylidium - Resources for Health Professionals".U.S. Centers for Disease Control and Prevention (CDC).21 May 2020.
^Remington JP, Osol A, eds. (1980).Remington's Pharmaceutical Sciences(16th ed.). Easton: Mack Pub. Co. p. 1182.OCLC 925174053.
^The Merck Manual of Diagnosis and Therapy(14th ed.). Rahway: Merck Sharp & Dohme Research Laboratories. 1982. p. 176.ISBN 978-0-911910-03-2.
^Weinbach EC, Garbus J (March 1969). "Mechanism of action of reagents that uncouple oxidative phosphorylation".Nature.221(5185): 1016–1018.Bibcode:1969Natur.221.1016W.doi:10.1038/2211016a0.PMID 4180173.S2CID 4209497.
^Boogaard, Michael A. Delivery Systems of Piscicideshttps://www.usbr.gov/lc/phoenix/biology/azfish/pdf/borfinalreport6t7.pdf.Archived(PDF)from the original on 2017-06-01.Retrieved2017-05-30.{{cite web}}:Missing or empty|title=(help)
^Verdel K.Dawson (2003). "Environmental Fate and Effects of the Lampricide Bayluscide: a Review".Journal of Great Lakes Research.29(Supplement 1): 475–492.Bibcode:2003JGLR...29..475D.doi:10.1016/S0380-1330(03)70509-7.
^^a ^b"WHO Specifications And Evaluations. For Public Health Pesticides. Niclosamide"(PDF).Archived fromthe original(PDF)on 2017-01-10.Retrieved2019-08-07.
^Blank L (30 October 2018)."Researchers find new methods to combat invasive zebra mussels".The Minnesota Daily.Archived fromthe originalon 2018-11-21.Retrieved2018-11-19.
^"Clinical Trials Using Niclosamide".NCI.Retrieved20 March2019.
^Rajamuthiah R, Fuchs BB, Conery AL, Kim W, Jayamani E, Kwon B, et al. (April 2015). Planet PJ (ed.)."Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus".PLOS ONE.10(4): e0124595.Bibcode:2015PLoSO..1024595R.doi:10.1371/journal.pone.0124595.PMC4405337.PMID 25897961.
^Li Y, Li P, He Q, Zhang R, Li Y, Kamar N, et al. (January 2022)."Niclosamide inhibits hepatitis E virus through suppression of NF-kappaB signalling".Antiviral Research.197:105228.doi:10.1016/j.antiviral.2021.105228.PMID 34929248.
^Braga L, Ali H, Secco I, Chiavacci E, Neves G, Goldhill D, et al. (June 2021)."Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia".Nature.594(7861): 88–93.Bibcode:2021Natur.594...88B.doi:10.1038/s41586-021-03491-6.PMC7611055.PMID 33827113.
^Barini E, Miccoli A, Tinarelli F, Mulholland K, Kadri H, Khanim F, et al. (March 2018)."The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1".ChemBioChem.19(5): 425–429.doi:10.1002/cbic.201700500.PMC5901409.PMID 29226533.

External links[edit]

"Niclosamide".Drug Information Portal.U.S. National Library of Medicine.
Niclosamidein the Pesticide Properties DataBase (PPDB)
"MedlinePlus Drug Information: Niclosamide (Oral)".MedlinePlus.U.S. National Library of Medicine. 1995-06-23. Archived fromthe originalon 2006-12-16.

[pubchem-1] CID 4477fromPubChem

[Cons2016-2] "Niclosamide Advanced Patient Information - Drugs.com".www.drugs.com.Archivedfrom the original on 20 December 2016.Retrieved8 December2016.

[WHO2008-3] World Health Organization(2009). Stuart MC, Kouimtzi M, Hill SR (eds.).WHO Model Formulary 2008.World Health Organization. pp. 81, 87, 591.hdl:10665/44053.ISBN 9789241547659.

[Riv2013-4] Lanusse CE, Alvarez LI, Sallovitz JM, Mottier ML, Sanchez Bruni SF (13 May 2013)."Antinematodal Drugs".In Riviere JE, Papich MG (eds.).Veterinary Pharmacology and Therapeutics.John Wiley & Sons. p. 1096.ISBN 978-1-118-68590-7.Archivedfrom the original on 10 September 2017.

[5] Mehlhorn H (2008).Encyclopedia of Parasitology: A-M.Springer Science & Business Media. p. 483.ISBN 978-3-540-48994-8.Archivedfrom the original on 2016-12-20.

[WHO21st-6] World Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.

[7] "Dipylidium - Resources for Health Professionals".U.S. Centers for Disease Control and Prevention (CDC).21 May 2020.

[8] Remington JP, Osol A, eds. (1980).Remington's Pharmaceutical Sciences(16th ed.). Easton: Mack Pub. Co. p. 1182.OCLC 925174053.

[9] The Merck Manual of Diagnosis and Therapy(14th ed.). Rahway: Merck Sharp & Dohme Research Laboratories. 1982. p. 176.ISBN 978-0-911910-03-2.

[pmid-10] Weinbach EC, Garbus J (March 1969). "Mechanism of action of reagents that uncouple oxidative phosphorylation".Nature.221(5185): 1016–1018.Bibcode:1969Natur.221.1016W.doi:10.1038/2211016a0.PMID 4180173.S2CID 4209497.

[11] Boogaard, Michael A. Delivery Systems of Piscicideshttps://www.usbr.gov/lc/phoenix/biology/azfish/pdf/borfinalreport6t7.pdf.Archived(PDF)from the original on 2017-06-01.Retrieved2017-05-30.{{cite web}}:Missing or empty|title=(help)

[12] Verdel K.Dawson (2003). "Environmental Fate and Effects of the Lampricide Bayluscide: a Review".Journal of Great Lakes Research.29(Supplement 1): 475–492.Bibcode:2003JGLR...29..475D.doi:10.1016/S0380-1330(03)70509-7.

[whodat-13] "WHO Specifications And Evaluations. For Public Health Pesticides. Niclosamide"(PDF).Archived fromthe original(PDF)on 2017-01-10.Retrieved2019-08-07.

[14] Blank L (30 October 2018)."Researchers find new methods to combat invasive zebra mussels".The Minnesota Daily.Archived fromthe originalon 2018-11-21.Retrieved2018-11-19.

[15] "Clinical Trials Using Niclosamide".NCI.Retrieved20 March2019.

[16] Rajamuthiah R, Fuchs BB, Conery AL, Kim W, Jayamani E, Kwon B, et al. (April 2015). Planet PJ (ed.)."Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus".PLOS ONE.10(4): e0124595.Bibcode:2015PLoSO..1024595R.doi:10.1371/journal.pone.0124595.PMC4405337.PMID 25897961.

[17] Li Y, Li P, He Q, Zhang R, Li Y, Kamar N, et al. (January 2022)."Niclosamide inhibits hepatitis E virus through suppression of NF-kappaB signalling".Antiviral Research.197:105228.doi:10.1016/j.antiviral.2021.105228.PMID 34929248.

[18] Braga L, Ali H, Secco I, Chiavacci E, Neves G, Goldhill D, et al. (June 2021)."Drugs that inhibit TMEM16 proteins block SARS-CoV-2 spike-induced syncytia".Nature.594(7861): 88–93.Bibcode:2021Natur.594...88B.doi:10.1038/s41586-021-03491-6.PMC7611055.PMID 33827113.

[19] Barini E, Miccoli A, Tinarelli F, Mulholland K, Kadri H, Khanim F, et al. (March 2018)."The Anthelmintic Drug Niclosamide and Its Analogues Activate the Parkinson's Disease Associated Protein Kinase PINK1".ChemBioChem.19(5): 425–429.doi:10.1002/cbic.201700500.PMC5901409.PMID 29226533.

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