Niclosamide

Niclosamide, sold under the brand name Niclocide among others, is a medication used to treat tapeworm infestations.[2] This includes diphyllobothriasis, hymenolepiasis, and taeniasis.[2] It is not effective against other worms such as pinworms or roundworms.[3] It is taken by mouth.[2]

Niclosamide
Clinical data
Trade namesNiclocide, Fenasal, Phenasal, others[1]
AHFS/Drugs.comMicromedex Detailed Consumer Information
Routes of
administration		By mouth
ATC code
Identifiers
IUPAC name
  • 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.052
Chemical and physical data
FormulaC13H8Cl2N2O4
Molar mass327.12 g·mol−1
3D model (JSmol)
Melting point225 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) Y
  • Key:RJMUSRYZPJIFPJ-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Side effects include nausea, vomiting, abdominal pain, and itchiness.[2] It may be used during pregnancy and appears to be safe for the baby.[2] Niclosamide is in the anthelmintic family of medications.[3] It works by blocking the uptake of sugar by the worm.[4]

Niclosamide was discovered in 1958.[5] It is on the World Health Organization's List of Essential Medicines.[6] It is not commercially available in the United States.[3] It is effective in a number of other animals.[4]

Side effects

Side effects include nausea, vomiting, abdominal pain, constipation, and itchiness.[2] 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. 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 in cysticercosis. Therefore, a purge should be given 1 or two hours after treatment. CNS cysticercosis is life-threatening condition and may require brain surgery. [7] [8]

Mechanism of action

Niclosamide inhibits glucose uptake, oxidative phosphorylation, and anaerobic metabolism in the tapeworm.[9]

Other applications

Niclosamide's metabolic effects are relevant to 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,[10][11] as a molluscide,[12] 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.[12] Researchers have found that niclosamide is effective in killing invasive zebra mussels in cool waters.[13]

Research

Niclosamide is being studied in a number of types of cancer.[14] Niclosamide along with oxyclozanide, another anti-tapeworm drug, was found in a 2015 study to display "strong in vivo and in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA)".[15]

Various studies have shown that Niclosamide has the potential to counteract various viral infections, at least in experimental conditions. For instance, it has been shown that it impairs the replication of Hepatitis E virus.[16] On July 1, 2020, Danish biotech company UNION started a clinical study using niclosamide in the treatment of COVID-19.[17]

Another study demonstrated the benefit of a combination of Niclosamide and ivermectin against SARS-CoV-2 activity, showing a synergistic profile, suggesting this combination should be further tested in clinical trials.[18]

There is another study that investigated the use of niclosamide as a treatment for COVID-19, showing effectiveness against virus replication and associated cytopathicity.[19]

In 2018, niclosamide was observed to be a potent activator of PTEN-induced kinase 1 in primary cortical neurons.[20] As PINK1 dysfunction is associated with a form of Parkinson's disease,[21] this quality makes niclosamide and derivative compounds attractive as research tools and potential treatment avenues for the condition.

References
  1. CID 4477 from PubChem
  2. 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.
  3. "Niclosamide Advanced Patient Information - Drugs.com". www.drugs.com. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
  4. Riviere JE, Papich MG (13 May 2013). Veterinary Pharmacology and Therapeutics. John Wiley & Sons. p. 1096. ISBN 978-1-118-68590-7. Archived from the original on 10 September 2017.
  5. Mehlhorn H (2008). Encyclopedia of Parasitology: A-M. Springer Science & Business Media. p. 483. ISBN 9783540489948. Archived from the original on 2016-12-20.
  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. Remingtons's Pharmaceutical Sciences, 16th edition, page 1182
  8. The Merck Manual of Diagnosis and Therapy, 14th edition, page 176
  9. Weinbach EC, Garbus J (1969). "Mechanism of action of reagents that uncouple oxidative phosphorylation". Nature. 221 (5185): 1016–8. Bibcode:1969Natur.221.1016W. doi:10.1038/2211016a0. PMID 4180173. S2CID 4209497.
  10. Boogaard, Michael A. Delivery Systems of Piscicides "Request Rejected" (PDF). Archived (PDF) from the original on 2017-06-01. Retrieved 2017-05-30.
  11. Verdel K.Dawson (2003). "Environmental Fate and Effects of the Lampricide Bayluscide: a Review". Journal of Great Lakes Research. 29 (Supplement 1): 475–492. doi:10.1016/S0380-1330(03)70509-7.
  12. "WHO Specifications And Evaluations. For Public Health Pesticides. Niclosamide" (PDF). Archived from the original (PDF) on 2017-01-10. Retrieved 2019-08-07.
  13. "Researchers find new methods to combat invasive zebra mussels". The Minnesota Daily. Retrieved 2018-11-19.
  14. "Clinical Trials Using Niclosamide". NCI. Retrieved 20 March 2019.
  15. Rajamuthiah R, Fuchs BB, Conery AL, Kim W, Jayamani E, Kwon B, Ausubel FM, Mylonakis E (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. ISSN 1932-6203. PMC 4405337. PMID 25897961.
  16. Li Y, Li P, He Q, Zhang R, Li Y, Kamar N, Peppelenbosch MP, de Man RA, Wang L, Pan Q (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.{{cite journal}}: CS1 maint: uses authors parameter (link)
  17. GmbH, finanzen net. "UNION Receives Approval From Danish Medicines Agency to Initiate Clinical Study With Niclosamide for Treatment of COVID-19 | Markets Insider". markets.businessinsider.com.
  18. Jitobaom, Kunlakanya; et al. (2022). "Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug combinations". BMC Pharmacol. Toxicol. 23 (41): 41. doi:10.1186/s40360-022-00580-8. PMC 9206137. PMID 35717393.
  19. Braga, Luca; Ali, Hashim; Secco, Ilaria; Chiavacci, Elena; Neves, Guilherme; Goldhill, Daniel; Penn, Rebecca; Jimenez-Guardeño, Jose M.; Ortega-Prieto, Ana M.; Bussani, Rossana; Cannatà, Antonio; Rizzari, Giorgia; Collesi, Chiara; Schneider, Edoardo; Arosio, Daniele; Shah, Ajay M.; Barclay, Wendy S.; Malim, Michael H.; Burrone, Juan; Giacca, Mauro (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. PMC 7611055. PMID 33827113.
  20. Barini E, Miccoli A, Tinarelli F, Mulholland K, Kadri H, Khanim F, Stojanovski L, Read KD, Burness K, Blow JJ, Mehellou Y, Muqit MMK (March 2, 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. PMC 5901409. PMID 29226533.{{cite journal}}: CS1 maint: uses authors parameter (link)
  21. "Entrez Gene: PINK1 PTEN induced putative kinase 1".
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.