Clioquinol (iodochlorhydroxyquin) tradename Entero-Vioform is an

antifungal drug An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as c ...

and

antiprotozoal Antiprotozoal agents ( ATC code: ATC P01) is a class of pharmaceuticals used in treatment of protozoan infection. A paraphyletic group, protozoans have little in common with each other. For example, '' Entamoeba histolytica'', a unikont eukary ...

drug. It is

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

in large doses. It is a member of a family of drugs called

hydroxyquinolines 8-Hydroxyquinoline (also known as oxine) is an organic compound derived from the heterocycle quinoline. A colorless solid, its conjugate base is a chelate, chelating agent, which is used for the Quantitative analysis (chemistry), quantitative det ...

which inhibit certain enzymes related to DNA replication. The drugs have been found to have activity against both

viral The word ''Viral'' means "relating to viruses" (small infectious agents). It may also refer to: Viral behavior, or virality Memetic behavior likened that of a virus, for example: * Viral marketing, the use of existing social networks to spre ...

and protozoal infections.

Antiprotozoal use

A 1964 report described the use of clioquinol in both the treatment and prevention of

shigella ''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...

infection and ''

Entamoeba histolytica ''Entamoeba histolytica'' is an anaerobic organism, anaerobic parasitic amoebozoan, part of the genus ''Entamoeba''. Predominantly infecting humans and other primates causing amoebiasis, ''E. histolytica'' is estimated to infect about 35-50 mil ...

'' 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 ''

'' infection. * A 2004 reference to its use in the Netherlands in the treatment of ''

Dientamoeba fragilis ''Dientamoeba fragilis'' is a species of single-celled excavates found in the gastrointestinal tract of some humans, pigs and gorillas. It causes gastrointestinal upset in some people, but not in others. It is an important cause of traveller's ...

'' infection. * A 1979 reference to the use in

Zaire Zaire, officially the Republic of Zaire, was the name of the Democratic Republic of the Congo from 1971 to 18 May 1997. Located in Central Africa, it was, by area, the third-largest country in Africa after Sudan and Algeria, and the 11th-la ...

in the treatment of ''

'' infection.

Subacute myelo-optic neuropathy

Clioquinol's use as an

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. 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 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.

Topical use

Clioquinol is a constituent of the prescription medicine Vioform, which is a topical

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...

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.

Potential use as a preventive or treatment in prostate cancer

It 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 In chemistry, an ionophore () is a chemical species that reversibly binds ions. Many ionophores are lipid-soluble entities that transport ions across the cell membrane. Ionophores catalyze ion transport across hydrophobic membranes, such as l ...

clioquinol was shown in mice to restore zinc levels and stop the growth of prostate tumors.

Use in neurodegenerative diseases

Research at

UCSF The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California, United States. It is part of the University of California system and is dedicated entirely to health science and life ...

indicates that clioquinol appears to block the genetic action of

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and ...

in mice and in cell culture. Recent animal studies have shown that clioquinol can reverse the progression of Alzheimer's,

Parkinson's Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalen ...

and Huntington's diseases. According to

Siegfried Hekimi Siegfried Hekimi (born 5 September 1956) is a Swiss former professional racing cyclist and a professor in the Biology Department of McGill University, specializing in the study of aging. He rode in the 1982 Tour de France. After his cycling car ...

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. 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.

Continued use and manufacture around the world

References

{{Agents against amoebozoa Antiprotozoal agents Antifungals Quinolinols Drugs developed by Novartis Iodoarenes Chloroarenes Otologicals