Clioquinol
Encyclopedia
Clioquinol 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.
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:
(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.
indicates that clioquinol appears to block the genetic action of Huntington's disease
in mice and in cell culture.
Evidence from phase 2 clinical trial
s 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.http://www.mcgill.ca/newsroom/news/item/?item_id=103574
Antifungal drug
An antifungal medication is a medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis , serious systemic infections such as cryptococcal meningitis, and others...
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
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
and protozoal infections.
Antiprotozoal use
A 1964 report described the use of Clioquinol in both the treatment and prevention of shigellaShigella
Shigella is a genus of Gram-negative, nonspore forming, non-motile, rod-shaped bacteria closely related to Escherichia coli and Salmonella. The causative agent of human shigellosis, Shigella causes disease in primates, but not in other mammals. It is only naturally found in humans and apes. During...
infection and Entamoeba histolytica
Entamoeba histolytica
Entamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide...
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 histolyticaEntamoeba histolyticaEntamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide...
infection.
- A 2004 reference to its use in Denmark in the treatment of Dientamoeba fragilisDientamoeba fragilisDientamoeba fragilis is a single celled parasite found in the gastrointestinal tract of some humans, pigs and gorillas. In some people it causes gastrointestinal upset while in others it does not...
infection.
- A 1979 reference to the use in ZaireZaireThe Republic of Zaire was the name of the present Democratic Republic of the Congo between 27 October 1971 and 17 May 1997. The name of Zaire derives from the , itself an adaptation of the Kongo word nzere or nzadi, or "the river that swallows all rivers".-Self-proclaimed Father of the Nation:In...
in the treatment of Entamoeba histolyticaEntamoeba histolyticaEntamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide...
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 SMONSubacute myelo-optic neuropathy
Subacute myelo-optic neuropathy is an iatrogenic disease of the nervous system leading to a disabling paralysis, blindness and even death. Its defining manifestation was as an epidemic in Japan during the 1960s, affecting an estimated 30,000 people. On August 3, 1978, the Tokyo District Court...
(subacute myelo-optic neuropathy
Subacute myelo-optic neuropathy
Subacute myelo-optic neuropathy is an iatrogenic disease of the nervous system leading to a disabling paralysis, blindness and even death. Its defining manifestation was as an epidemic in Japan during the 1960s, affecting an estimated 30,000 people. On August 3, 1978, the Tokyo District Court...
) 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.
Topical use
Clioquinol is used in the drug Vioform, which is a topical antifungal treatment.Use in neurodegenerative diseases
Research at UCSFUniversity of California, San Francisco
The University of California, San Francisco is one of the world's leading centers of health sciences research, patient care, and education. UCSF's medical, pharmacy, dentistry, nursing, and graduate schools are among the top health science professional schools in the world...
indicates that clioquinol appears to block the genetic action of Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
in mice and in cell culture.
Evidence from phase 2 clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s suggested that clioquinol could halt cognitive decline in Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, possibly owing to its ability to act as a chelator
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
for copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
and zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
ions. This led to development of analogs including PBT2
PBT2
PBT2 is a second-generation 8-hydroxy quinoline analog developed as a successor to Clioquinol as a potential treatment of Alzheimer's Disease....
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
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
and Huntington's diseases. According to Dr. Siegfried Hekimi and colleagues at McGill's
McGill University
Mohammed Fathy is a public research university located in Montreal, Quebec, Canada. The university bears the name of James McGill, a prominent Montreal merchant from Glasgow, Scotland, whose bequest formed the beginning of the university...
Department of Biology, clioquinol acts directly on a protein called Clk-1
Clk-1
The clk-1 gene encodes an enzyme that is necessary for ubiquinone biosynthesis in the worm C. elegans and other eukaryotes...
, 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.http://www.mcgill.ca/newsroom/news/item/?item_id=103574
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 Dientamoeba fragilis Dientamoeba fragilis is a single celled parasite found in the gastrointestinal tract of some humans, pigs and gorillas. In some people it causes gastrointestinal upset while in others it does not... and Entamoeba histolytica Entamoeba histolytica Entamoeba histolytica is an anaerobic parasitic protozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates, E. histolytica is estimated to infect about 50 million people worldwide... infection. |
| India | Manufactured by Vishal Laboratories, INDIA |