Clioquinol

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Clioquinol
Skeletal formula of clioquinol
Ball-and-stick model of the clioquinol molecule
Systematic (IUPAC) name
5-Chloro-7-iodo-quinolin-8-ol
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a682367
Pregnancy
category
  • US: C (Risk not ruled out) [1]
Legal status
Routes of
administration		 topical only
Identifiers
CAS Number 130-26-7 YesY
ATC code D08AH30 (WHO)
D09AA10 (dressing) G01AC02 P01AA02 S02AA05
PubChem CID: 2788
DrugBank DB04815 YesY
ChemSpider 2686 YesY
UNII 7BHQ856EJ5 YesY
KEGG D03538 YesY
ChEBI CHEBI:74460 N
ChEMBL CHEMBL497 YesY
Chemical data
Formula C9H5ClINO
Molecular mass 305.50 g·mol−1
  • Ic1c(O)c2ncccc2c(Cl)c1
  • InChI=1S/C9H5ClINO/c10-6-4-7(11)9(13)8-5(6)2-1-3-12-8/h1-4,13H YesY
  • Key:QCDFBFJGMNKBDO-UHFFFAOYSA-N YesY
 NYesY (what is this?)  (verify)

Clioquinol (iodochlorhydroxyquin) 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.[2]

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.[3]

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

Clioquinol and SMON

Lua error in package.lua at line 80: module 'strict' not found. 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.[7] 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.[8] Theories suggested have included improper dosing, the permitted use of the drug for extended periods of time,[9] and dosing which did not consider the smaller average stature of Japanese; however a dose dependant relationship between SMON development and clioquinol use was never found, suggesting the interaction of another compound. Researchers have also suggested the SMON epidemic could have been due to a viral infection with an Inoue-Melnick virus.[10]

Topical use

Clioquinol is a constituent of the prescription medicine Vioform, which is a topical antifungal treatment. It is also used in the form of a cream (and in combination with betamethasone) in the treatment of inflammatory skin disorders.

Use in neurodegenerative diseases

Research at UCSF indicates that clioquinol appears to block the genetic action of Huntington's disease in mice and in cell culture.[11]

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.[12]

Recent animal studies have shown that clioquinol can reverse the progression of Alzheimer's, Parkinson's and Huntington's diseases. According to Dr. Siegfried Hekimi and colleagues at McGill's Department of Biology, clioquinol acts directly on a protein called Clk-1, often informally called “clock-1,” and might slow down the aging process. They theorize that this may explain the apparent ability of the drug to be effective in the above conditions, but warn against individuals experimenting with this drug.[13]

Use for autism

Research at the Academica Sinica in Taiwan shows that Clioquinol may be effective in increasing the transmission of zinc to the brain, thereby correcting the zinc deficiency found in many children with autism. When this was done to mice displaying autistic behaviour, their autistic traits subsided and their behaviour became almost identical to that of mice who were not autistic. The Academica Sinica researchers hope that psychiatrists will consider prescribing the drug, which is already permitted in Taiwan, to suitable patients.[14]

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 each other's 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.
Netherlands 2004 and 2005 reports describe use in treatment of Dientamoeba fragilis and Entamoeba histolytica infection.[5][5]
India Manufactured by Vishal Laboratories and LASA Laboratory[15]

See also

  • PBT2, a related 8-hydroxyquinoline

References

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  12. ↑ Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta.
  13. ↑ [1]
  14. ↑ [2]
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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