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{{DrugProjectFormSinglePage
{{Drugbox|
|authorTag=<!--Overview-->
|IUPAC_name = 5-chloro-7-iodo-quinolin-8-ol
|aOrAn=a
| image = Clioquinol.png
|hasBlackBoxWarning=Yes
| CAS_number=130-26-7
|adverseReactions=<!--Black Box Warning-->
| ATC_prefix=D08
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====Signs and Symptoms====
 
* Description


====Management====
{{SI}}
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===Chronic Overdose===


There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
==Overview==
'''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.<ref name="pmid185949">{{cite journal |author=Rohde W, Mikelens P, Jackson J, Blackman J, Whitcher J, Levinson W |title=Hydroxyquinolines inhibit ribonucleic acid-dependent deoxyribonucleic acid polymerase and inactivate Rous sarcoma virus and herpes simplex virus |journal=Antimicrob. Agents Chemother. |volume=10 |issue=2 |pages=234-40 |year=1976 |pmid=185949 |doi=}}</ref>


<!--Pharmacology-->
==Antiprotozoal use==


<!--Drug box 2-->
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. <ref name="pmid14162901">{{cite journal |author=GHOLZ LM, ARONS WL |title=PROPHYLAXIS AND THERAPY OF AMEBIASIS AND SHIGELLOSIS WITH IODOCHLORHYDROXYQUIN |journal=Am. J. Trop. Med. Hyg. |volume=13 |issue= |pages=396-401 |year=1964 |pmid=14162901 |doi=}}</ref>
|drugBox=<!--Mechanism of Action-->
|mechAction=*


<!--Structure-->
Several recently reported journal articles describing its use as an antiprotozoal include:
|structure=*


: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
* A 2005 reference to its use in treating a Dutch family for ''[[Entamoeba histolytica]]'' infection. <ref name="pmid15651505">{{cite journal |author=Kager PA |title=[Outbreak of amoebiasis in a Dutch family; tropics unexpectedly nearby] |language=Dutch; Flemish |journal=Nederlands tijdschrift voor geneeskunde |volume=149 |issue=1 |pages=51-2; author reply 52-3 |year=2005 |pmid=15651505 |doi=}}</ref>


<!--Pharmacodynamics-->
* A 2004 reference to its use in Denmark in the treatment of ''[[Dientamoeba fragilis]]'' infection.<ref name="pmid15074181">{{cite journal |author=Bosman DK, Benninga MA, van de Berg P, Kooijman GC, van Gool T |title=[Dientamoeba fragilis: possibly an important cause of persistent abdominal pain in children] |language=Dutch; Flemish |journal=Nederlands tijdschrift voor geneeskunde |volume=148 |issue=12 |pages=575-9 |year=2004 |pmid=15074181 |doi=}}</ref>
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.


<!--Pharmacokinetics-->
* A 1979 reference to the use in Zaire in the treatment of ''[[Entamoeba histolytica]]'' infection. <ref name="pmid226725">{{cite journal |author=Masters DK, Hopkins AD |title=Therapeutic trial of four amoebicide regimes in rural Zaire |journal=The Journal of tropical medicine and hygiene |volume=82 |issue=5 |pages=99-101 |year=1979 |pmid=226725 |doi=}}</ref>
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.


<!--Nonclinical Toxicology-->
==Clioquinol and SMON==
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.


<!--Clinical Studies-->
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 [[Subacute myelo-optic neuropathy|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.<ref name="pmid6091394">{{cite journal |author=Wadia NH |title=SMON as seen from Bombay |journal=Acta Neurol. Scand., Suppl. |volume=100 |issue= |pages=159-64 |year=1984 |pmid=6091394 |doi=}}</ref>  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.<ref name="pmid127638">{{cite journal |author=Meade TW |title=Subacute myelo-optic neuropathy and clioquinol. An epidemiological case-history for diagnosis |journal=British journal of preventive & social medicine |volume=29 |issue=3 |pages=157-69 |year=1975 |pmid=127638 |doi=}}</ref>  Theories suggested have included improper dosing, the permitted use of the drug for extended periods of time, <ref name="pmid15152488">{{cite journal |author=Takasu T |title=[SMON--a model of the iatrogenic disease] |language=Japanese |journal=Rinsho Shinkeigaku |volume=43 |issue=11 |pages=866-9 |year=2003 |pmid=15152488 |doi=}}</ref> and dosing which did not consider the smaller average stature of Japanese.  Researchers have also suggested the SMON epidemic could have been due to a viral infection with a Inoue-Melnick virus.<ref name="pmid9625419">{{cite journal |author=Ito M, Nishibe Y, Inoue YK |title=Isolation of Inoue-Melnick virus from cerebrospinal fluid of patients with epidemic neuropathy in Cuba |journal=Arch. Pathol. Lab. Med. |volume=122 |issue=6 |pages=520-2 |year=1998 |pmid=9625419 |doi=}}</ref>
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.


<!--How Supplied-->
==Topical use==
|howSupplied=*
|packLabel=<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.


<!--Precautions with Alcohol-->
Clioquinol is used in the drug Vioform, which is a topical [[antifungal]] treatment.
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.


<!--Brand Names-->
==Use in neurodegenerative diseases==
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>


<!--Look-Alike Drug Names-->
Recent research at UCSF indicates that clioquinol appears to block the genetic action of [[Huntington's disease]] in mice and in cell culture.<ref>{{cite journal |author=Nguyen T, Hamby A, Massa SM |title=Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=102 |issue=33 |pages=11840-5 |year=2005 |pmid=16087879 |doi=10.1073/pnas.0502177102}}</ref>
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web  | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>


<!--Drug Shortage Status-->
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 [[chelation|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.
|drugShortage=
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==Continued use and manufacture around the world==




<!--Label Display Image-->
{| class="wikitable"
|-
! Country
! Comments
|-
| United States
| In August 2004, [http://www.pranabio.com/ Prana Biotechnology], an Australian company and P.N Gerolymatos S.A (PNG) agreed to recognize eachothers 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. <ref name="pmid15074181" /> <ref name="pmid15074181" />
|-
| India
| Manufactured by [http://www.salvichem.com/ Salvichem]
|-
|}


==References==
{{Reflist|2}}


[[Category:Antiprotozoal agents]]


[[Category:Antifungals]]
[[Category:Quinolines]]
[[Category:Organohalides]]




<!--Category-->
{{Antiseptics and disinfectants}}
{{Medicated dressings}}
{{Gynecological anti-infectives and antiseptics}}
{{Otologicals}}


[[Category:Drug]]
{{WH}}
{{WS}}

Latest revision as of 15:29, 4 February 2015

Clioquinol
Clinical data
Routes of
administration		topical only
ATC code
Legal status
Legal status
  • PoM (UK); Rx (US)
Identifiers
CAS Number
PubChem CID
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC9H5ClINO
Molar mass305.499 g/mol

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

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.[1]

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. [2]

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.[6] 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.[7] Theories suggested have included improper dosing, the permitted use of the drug for extended periods of time, [8] and dosing which did not consider the smaller average stature of Japanese. Researchers have also suggested the SMON epidemic could have been due to a viral infection with a Inoue-Melnick virus.[9]

Topical use

Clioquinol is used in the drug Vioform, which is a topical antifungal treatment.

Use in neurodegenerative diseases

Recent research at UCSF indicates that clioquinol appears to block the genetic action of Huntington's disease in mice and in cell culture.[10]

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.

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 eachothers 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. [4] [4]
India Manufactured by Salvichem

References

  1. ↑ 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. PMID 185949.
  2. ↑ GHOLZ LM, ARONS WL (1964). "PROPHYLAXIS AND THERAPY OF AMEBIASIS AND SHIGELLOSIS WITH IODOCHLORHYDROXYQUIN". Am. J. Trop. Med. Hyg. 13: 396–401. PMID 14162901.
  3. ↑ Kager PA (2005). "[Outbreak of amoebiasis in a Dutch family; tropics unexpectedly nearby]". Nederlands tijdschrift voor geneeskunde (in Dutch; Flemish). 149 (1): 51–2, author reply 52-3. PMID 15651505.
  4. ↑ 4.0 4.1 4.2 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]". Nederlands tijdschrift voor geneeskunde (in Dutch; Flemish). 148 (12): 575–9. PMID 15074181.
  5. ↑ 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.
  6. ↑ Wadia NH (1984). "SMON as seen from Bombay". Acta Neurol. Scand., Suppl. 100: 159–64. PMID 6091394.
  7. ↑ 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. PMID 127638.
  8. ↑ Takasu T (2003). "[SMON--a model of the iatrogenic disease]". Rinsho Shinkeigaku (in Japanese). 43 (11): 866–9. PMID 15152488.
  9. ↑ 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.
  10. ↑ 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. PMID 16087879.


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