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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/06/10 14:58:04」(JST)

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Clioquinol

Systematic (IUPAC) name
5-Chloro-7-iodo-quinolin-8-ol
Clinical data
Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a682367
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	topical only
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Identifiers
CAS Number	130-26-7 Y
ATC code	D08AH30 (WHO) D09AA10 (WHO) (dressing) G01AC02 (WHO) P01AA02 (WHO) S02AA05 (WHO)
PubChem	CID 2788
DrugBank	DB04815 Y
ChemSpider	2686 Y
UNII	7BHQ856EJ5 Y
KEGG	D03538 Y
ChEBI	CHEBI:74460 N
ChEMBL	CHEMBL497 Y
Chemical data
Formula	C9H5ClINO
Molar mass	305.50 g·mol−1
SMILES Ic1c(O)c2ncccc2c(Cl)c1
InChI InChI=1S/C9H5ClINO/c10-6-4-7(11)9(13)8-5(6)2-1-3-12-8/h1-4,13H Y Key:QCDFBFJGMNKBDO-UHFFFAOYSA-N Y
NY (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.

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.

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

• A 2005 reference to its use in treating a Dutch family for Entamoeba histolytica infection.
• A 2004 reference to its use in the Netherlands in the treatment of Dientamoeba fragilis infection.
• A 1979 reference to the use in Zaire in the treatment of Entamoeba histolytica infection.

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. 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. Theories suggested have included improper dosing, the permitted use of the drug for extended periods of time, 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.

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.

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.

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.

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.
India	Manufactured by Vishal Laboratories and LASA Laboratory

See also

• PBT2, a related 8-hydroxyquinoline

References

English Journal

• Navigating the Chemical Space of Multitarget-Directed Ligands: From Hybrids to Fragments in Alzheimer's Disease.

• Prati F1,2, Cavalli A3,4, Bolognesi ML5.
• Molecules (Basel, Switzerland).Molecules.2016 Apr 8;21(4). pii: E466. doi: 10.3390/molecules21040466.
• Multitarget drug discovery is one of the hottest topics and most active fields in the search for new molecules against Alzheimer's disease (AD). Over the last 20 years, many promising multitarget-directed ligands (MTDLs) have been identified and developed at a pre-clinical level. However, how to des
• PMID 27070562

• Combination treatment with fasudil and clioquinol produces synergistic anti-tumor effects in U87 glioblastoma cells by activating apoptosis and autophagy.

• He M1, Luo M2, Liu Q3, Chen J4, Li K1, Zheng M1, Weng Y1, Ouyang L1, Liu A5.
• Journal of neuro-oncology.J Neurooncol.2016 Apr;127(2):261-70. doi: 10.1007/s11060-015-2044-2. Epub 2016 Jan 2.
• Survival of patients with glioblastoma (GBM) remains poor, and novel treatment methods are urgently needed. In this study, we tested the effects of a combination of fasudil, a ROCK inhibitor, and clioquinol, an 8-hydroxyquinoline derivative with antimicrobial properties, on human GBM U87 cells. Comb
• PMID 26725099

• Disulfiram when combined with copper enhances the therapeutic effects of temozolomide for the treatment of Glioblastoma.

• Lun X1, Wells JC2, Grinshtein N3, King JC2, Hao X4, Dang NH2, Wang X4, Aman A5, Uehling D5, Datti A6, Wrana JL7, Easaw JC8, Luchman A9, Weiss S10, Cairncross JG10, Kaplan DR11, Robbins SM12, Senger DL13.
• Clinical cancer research : an official journal of the American Association for Cancer Research.Clin Cancer Res.2016 Mar 22. pii: clincanres.1798.2015. [Epub ahead of print]
• PURPOSE: Glioblastoma is one of the most lethal cancers in humans, and with existing therapy, survival remains at 14.6 months. Current barriers to successful treatment include their infiltrative behavior, extensive tumor heterogeneity, and the presence of a stem-like population of cells, termed brai
• PMID 27006494

Japanese Journal

• Pharmacovigilance における個と集団

• 薬剤疫学 20(1), 35-39, 2015
• NAID 130005099431

• Changes of ultrasonic bone assessment in subacute myelo-optico-neuropathy (SMON) patients (骨粗鬆症の診断と治療)

• オステオポローシスジャパン 19(3), 519-526, 2011
• NAID 40018957867

• 神経学の発展と社会貢献

• 臨床神経学 49(11), 741-744, 2009-11-01
• NAID 10026290685

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• スモン SMON：下痢症を伴う脳脊髄炎症、視力障害、知覚異常、運動障害

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