Clioquinol (iodochlorhydroxyquin) tradename Entero-Vioform 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]
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| Trade names | Cortin |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| MedlinePlus | a682367 |
| Routes of administration | topical only |
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| ECHA InfoCard | 100.004.533 |
| Chemical and physical data | |
| Formula | C9H5ClINO |
| Molar mass | 305.50 g·mol−1 |
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Antiprotozoal use
editA 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:
- A 2005 reference to its use in treating a Dutch family for Entamoeba histolytica infection.[4]
- A 2004 reference to its use in the Netherlands in the treatment of Dientamoeba fragilis infection.[5]
- A 1979 reference to the use in Zaire in the treatment of Entamoeba histolytica infection.[6]
Subacute myelo-optic neuropathy
editClioquinol'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 subacute myelo-optic neuropathy (SMON) 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 dependent 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
editClioquinol 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 or fluocinolone) in the treatment of inflammatory skin disorders.[citation needed]
Potential use as a preventive or treatment in prostate cancer
editIt has long been recognized that normal prostate cells have high zinc content through ZIP1 mediated uptake, and have low respiration (OXPHOS ATP generation is diverted to citrate export for sperm energetics). Prostate cancer cells have downregulated ZIP1 transporters which leads to greater ATP generation which is diverted to cancer proliferation, an example of a normal-like metabolic phenotype instead being malignant. The zinc ionophore clioquinol was shown in mice to restore zinc levels and stop the growth of prostate tumors.[11]
Use in neurodegenerative diseases
editResearch at UCSF indicates that clioquinol appears to block the genetic action of Huntington's disease in mice and in cell culture.[12]
Recent animal studies have shown that clioquinol can reverse the progression of Alzheimer's, Parkinson's and Huntington's diseases.[13] According to 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.[14]
In addition, a study performed in Drosophila demonstrates that clioquinol can slow the pathogenesis of tauopathy model by removing the excessive zinc in the cell.[15]
Continued use and manufacture around the world
edit| 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. |
| 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] |
| India | Manufactured by Eskay Iodine Pvt. Ltd., Vishal Laboratories, DNS Fine Chemicals[16] and LASA Laboratory[17] |
| Colombia | Manufactured by "Altea Farmacéutica C.A." for "Scandinavia Pharma"[18] |
See also
editReferences
edit- ^ "Clioquinol topical medical facts from Drugs.com". drugs.com. Retrieved 15 May 2015.
- ^ Rohde W, Mikelens P, Jackson J, Blackman J, Whitcher J, Levinson W (August 1976). "Hydroxyquinolines inhibit ribonucleic acid-dependent deoxyribonucleic acid polymerase and inactivate Rous sarcoma virus and herpes simplex virus". Antimicrobial Agents and Chemotherapy. 10 (2): 234–240. doi:10.1128/aac.10.2.234. PMC 429727. PMID 185949.
- ^ Gholz LM, Arons WL (May 1964). "Prophylaxis and Therapy of Amebiasis and Shigellosis with Iodochlorhydroxyquin". The American Journal of Tropical Medicine and Hygiene. 13 (3): 396–401. doi:10.4269/ajtmh.1964.13.396. PMID 14162901.
- ^ Kager PA (January 2005). "[Outbreak of amoebiasis in a Dutch family; tropics unexpectedly nearby]". Nederlands Tijdschrift voor Geneeskunde (in Dutch). 149 (1): 51–2, author reply 52–3. PMID 15651505.
- ^ a b Bosman DK, Benninga MA, van de Berg P, Kooijman GC, van Gool T (March 2004). "[Dientamoeba fragilis: possibly an important cause of persistent abdominal pain in children]". Nederlands Tijdschrift voor Geneeskunde (in Dutch). 148 (12): 575–579. PMID 15074181.
- ^ Masters DK, Hopkins AD (May 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 Neurologica Scandinavica. Supplementum. 100: 159–164. PMID 6091394.
- ^ Meade TW (September 1975). "Subacute myelo-optic neuropathy and clioquinol. An epidemiological case-history for diagnosis". British Journal of Preventive & Social Medicine. 29 (3): 157–169. doi:10.1136/jech.29.3.157. PMC 478909. PMID 127638.
- ^ Takasu T (November 2003). "[SMON--a model of the iatrogenic disease]". Rinsho Shinkeigaku = Clinical Neurology (in Japanese). 43 (11): 866–869. PMID 15152488.
- ^ Ito M, Nishibe Y, Inoue YK (June 1998). "Isolation of Inoue-Melnick virus from cerebrospinal fluid of patients with epidemic neuropathy in Cuba". Archives of Pathology & Laboratory Medicine. 122 (6): 520–522. PMID 9625419.
- ^ Costello LC, Franklin RB (December 2016). "A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer". Archives of Biochemistry and Biophysics. 611 (1): 100–112. doi:10.1016/j.abb.2016.04.014. PMC 5083243. PMID 27132038.
- ^ Nguyen T, Hamby A, Massa SM (August 2005). "Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model". Proceedings of the National Academy of Sciences of the United States of America. 102 (33): 11840–11845. Bibcode:2005PNAS..10211840N. doi:10.1073/pnas.0502177102. PMC 1187967. PMID 16087879.
- ^ Adlard PA, Cherny RA, Finkelstein DI, Gautier E, Robb E, Cortes M, et al. (July 2008). "Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta". Neuron. 59 (1): 43–55. doi:10.1016/j.neuron.2008.06.018. PMID 18614028. S2CID 17263833.
- ^ "News: Old gastrointestinal drug slows aging, McGill researchers say". Archived from the original on 2011-02-10. Retrieved 2017-08-25.
- ^ Huang Y, Wu Z, Cao Y, Lang M, Lu B, Zhou B (August 2014). "Zinc binding directly regulates tau toxicity independent of tau hyperphosphorylation". Cell Reports. 8 (3): 831–842. doi:10.1016/j.celrep.2014.06.047. PMC 4306234. PMID 25066125.
- ^ "Manufacturers of Clioquinol". DNS Fine Chemicals. 2016-01-06. Retrieved 23 December 2017.
- ^ Herlekar O. "Clioquinol manufacturers India". Lasa labs. Archived from the original on 29 June 2019. Retrieved 12 March 2013.
- ^ "Dermosupril C 0,1% desonide + 3% clioquinol for topical use" (PDF). Medihealth laboratories. Retrieved 19 September 2016.