Clioquinol Systematic (IUPAC) name 5-chloro-7-iodo-quinolin-8-ol Clinical data AHFS/Drugs.com MedlinePlus Pregnancy cat. ? Legal status PoM (UK); Rx (US) Routes topical only Identifiers CAS number ATC code D08 D09 G01 P01 S02 PubChem DrugBank ChemSpider UNII KEGG ChEMBL Chemical data Formula C9H5ClINO Mol. mass 305.499 g/mol SMILES & (what is this?)
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.
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:
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 a Inoue-Melnick virus.
Clioquinol is used in the drug Vioform, which is a topical antifungal treatment.
Use in neurodegenerative diseases
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 others 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.   India Manufactured by Vishal Laboratories, INDIA
- ^ 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. PMC 429727. PMID 185949. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=429727.
- ^ GHOLZ LM, ARONS WL (1964). "Prophylaxis And Therapy Of Amebiasis And Shigellosis With Iodochlorhydroxyquin". Am. J. Trop. Med. Hyg. 13: 396–401. PMID 14162901.
- ^ Kager PA (2005). "[Outbreak of amoebiasis in a Dutch family; tropics unexpectedly nearby]" (in Dutch; Flemish). Nederlands tijdschrift voor geneeskunde 149 (1): 51–2; author reply 52–3. PMID 15651505.
- ^ a b c 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]" (in Dutch; Flemish). Nederlands tijdschrift voor geneeskunde 148 (12): 575–9. PMID 15074181.
- ^ 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.
- ^ Wadia NH (1984). "SMON as seen from Bombay". Acta Neurol. Scand., Suppl. 100: 159–64. PMID 6091394.
- ^ 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. PMC 478909. PMID 127638. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=478909.
- ^ Takasu T (2003). "[SMON--a model of the iatrogenic disease]" (in Japanese). Rinsho Shinkeigaku 43 (11): 866–9. PMID 15152488.
- ^ 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.
- ^ 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. doi:10.1073/pnas.0502177102. PMC 1187967. PMID 16087879. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1187967.
- ^ Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta.
Antiseptics and disinfectants (D08) Acridine derivatives Biguanides and amidines Phenol and derivatives Nitrofuran derivativesNitrofurazone Iodine products Quinoline derivatives Quaternary ammonium compounds Mercurial products Silver compounds Alcohols Other Medicated dressings (D09) Ointment dressings
Other Gynecological anti-infectives and antiseptics (G01) Antibiotics Arsenic compounds Quinoline derivatives Organic acids SulfonamidesSulfatolamide Imidazole derivatives Triazole derivatives Other Otologicals (S02) Anti-infectives Corticosteroids Analgesics and anesthetics
Antiparasitics – antiprotozoal agents – agents against amoebozoa/amebicide (P01) EntamoebaNitroimidazole derivativesOtherHydroxyquinoline derivativesDichloroacetamide derivativesOther/ungrouped Acanthamoeba
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