Clioquinol

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Clioquinol
Systematic (IUPAC) name
5-chloro-7-iodo-quinolin-8-ol
Identifiers
CAS number 130-26-7
ATC code D08AH30 D09AA10 G01AC02 P01AA02 S02AA05
PubChem 2788
Chemical data
Formula C9H5ClINO 
Mol. mass 305.499 g/mol
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.

?

Legal status

PoM (UK); Rx (US)

Routes topical only

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

Clioquinol is an antifungal drug and antiprotozoal drug. It is neurotoxic in large doses. It is a member of a family of drugs called hydroxyquinolines which inhibit certain enzymes related to DNA replication. The drugs have been found to have activity against both viral and protozoal infections.[1]

Antiprotozoal use

A 1964 report described the use of Clioquinol in both the treatment and prevention of shigella infection and Entamoeba histolytica infection in institutionalized individuals at Sonoma State Hospital in California. The report indicates 4000 individuals were treated over a 4-year period with few side effects. [2]

Several recently reported journal articles describing its use as an antiprotozoal include:

Clioquinol and SMON

Clioquinol's use as an antiprotozoal drug has been restricted or discontinued in some countries due to an event in Japan where over 10,000 people developed SMON (subacute myelo-optic neuropathy) between 1957 and 1970. The drug was used widely in many countries before and after the SMON event without similar reports.[6] As yet, no explanation exists as to why it produced this reaction, and some researchers have questioned whether clioquinol was the causative agent in the disease, noting that the drug had been used for 20 years prior to the epidemic without incident, and that the SMON cases began to reduce in number prior to the discontinuation of the drug.[7] Theories suggested have included improper dosing, the permitted use of the drug for extended periods of time, [8] and dosing which did not consider the smaller average stature of Japanese. Researchers have also suggested the SMON epidemic could have been due to a viral infection with a Inoue-Melnick virus.[9]

Topical use

Clioquinol is used in the drug Vioform, which is a topical antifungal treatment.

Use in neurodegenerative diseases

Recent research at UCSF indicates that clioquinol appears to block the genetic action of Huntington's disease in mice and in cell culture.[10]

Evidence from phase 2 clinical trials suggested that clioquinol could halt cognitive decline in Alzheimer's disease, possibly owing to its ability to act as a chelator for copper and zinc ions. This led to development of analogs including PBT2 as potential therapeutic compounds for the treatment of Alzheimer's disease.

Continued use and manufacture around the world

Country Comments
United States In August 2004, Prana Biotechnology, an Australian company and P.N Gerolymatos S.A (PNG) agreed to recognize eachothers rights to market Clioquinol in their respective territories, with PNG holding right for European territories, and Prana holding rights for US and Japan. Prana has performed research into the use of Hydroxyquinolines drugs in the treatment of Alzheimers disease.
Canada In 2001, the Canadian company Paladin Labs bought the rights to market Vioform from Novartis.

Vioform is licensed for use in Canada as a topical anti-fungal.

Denmark 2004 and 2005 reports describe use in treatment of Dientamoeba fragilis and Entamoeba histolytica infection. [4] [4]
India Manufactured by Salvichem

References

  1. Rohde W, Mikelens P, Jackson J, Blackman J, Whitcher J, Levinson W (1976). "Hydroxyquinolines inhibit ribonucleic acid-dependent deoxyribonucleic acid polymerase and inactivate Rous sarcoma virus and herpes simplex virus". Antimicrob. Agents Chemother. 10 (2): 234–40. PMID 185949. 
  2. GHOLZ LM, ARONS WL (1964). "PROPHYLAXIS AND THERAPY OF AMEBIASIS AND SHIGELLOSIS WITH IODOCHLORHYDROXYQUIN". Am. J. Trop. Med. Hyg. 13: 396–401. PMID 14162901. 
  3. Kager PA (2005). "[Outbreak of amoebiasis in a Dutch family; tropics unexpectedly nearby]". Nederlands tijdschrift voor geneeskunde (in Dutch; Flemish). 149 (1): 51–2; author reply 52–3. PMID 15651505. 
  4. 4.0 4.1 4.2 Bosman DK, Benninga MA, van de Berg P, Kooijman GC, van Gool T (2004). "[Dientamoeba fragilis: possibly an important cause of persistent abdominal pain in children]". Nederlands tijdschrift voor geneeskunde (in Dutch; Flemish). 148 (12): 575–9. PMID 15074181. 
  5. Masters DK, Hopkins AD (1979). "Therapeutic trial of four amoebicide regimes in rural Zaire". The Journal of tropical medicine and hygiene. 82 (5): 99–101. PMID 226725. 
  6. Wadia NH (1984). "SMON as seen from Bombay". Acta Neurol. Scand., Suppl. 100: 159–64. PMID 6091394. 
  7. Meade TW (1975). "Subacute myelo-optic neuropathy and clioquinol. An epidemiological case-history for diagnosis". British journal of preventive & social medicine. 29 (3): 157–69. PMID 127638. 
  8. Takasu T (2003). "[SMON--a model of the iatrogenic disease]". Rinsho Shinkeigaku (in Japanese). 43 (11): 866–9. PMID 15152488. 
  9. Ito M, Nishibe Y, Inoue YK (1998). "Isolation of Inoue-Melnick virus from cerebrospinal fluid of patients with epidemic neuropathy in Cuba". Arch. Pathol. Lab. Med. 122 (6): 520–2. PMID 9625419. 
  10. Nguyen T, Hamby A, Massa SM (2005). "Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model". Proc. Natl. Acad. Sci. U.S.A. 102 (33): 11840–5. PMID 16087879. doi:10.1073/pnas.0502177102. 




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