Clioquinol: Difference between revisions

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{{Drugbox|
{{Drugbox
|IUPAC_name = 5-chloro-7-iodo-quinolin-8-ol
| Verifiedfields = changed
| image = Clioquinol.png
| verifiedrevid = 460018936
| CAS_number=130-26-7
| IUPAC_name = (5''Z'',9α,11α,13''E'',15''S'')-9,11,15-trihydroxy-15- methylprosta-5,13-dien-1-oic acid
| ATC_prefix=D08
| image = Carboprost.svg
| ATC_suffix=AH30
| ATC_supplemental={{ATC|D09|AA10}} {{ATC|G01|AC02}} {{ATC|P01|AA02}} {{ATC|S02|AA05}}
| PubChem=2788
| DrugBank=
| C=9|H=5|Cl=1|I=1|N=1|O=1
| molecular_weight = 305.499 g/mol
| bioavailability=
| metabolism =
| elimination_half-life=
| excretion = 
| pregnancy_category =
| legal_status = PoM (UK); Rx (US)
| routes_of_administration= topical only
}}


{{SI}}
<!--Clinical data-->
{{CMG}}
| tradename = 
| Drugs.com = {{drugs.com|CONS|carboprost}}
| MedlinePlus = a600042
| pregnancy_category = c
| legal_status = Rx-only
| routes_of_administration = Intramuscular


<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 


<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 58551-69-2
| ATC_prefix = G02
| ATC_suffix = AD04
| ATC_supplemental = 
| PubChem = 5281075
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00429
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4444532
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = U4526F86FJ
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1237122


==Overview==
<!--Chemical data-->
'''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>
| C=21 | H=36 | O=5
 
| molecular_weight = 368.508 g/mol
==Antiprotozoal use==
| smiles = O=C(O)CCC/C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1/C=C/[C@](O)(C)CCCCC
 
| InChI = 1/C21H36O5/c1-3-4-9-13-21(2,26)14-12-17-16(18(22)15-19(17)23)10-7-5-6-8-11-20(24)25/h5,7,12,14,16-19,22-23,26H,3-4,6,8-11,13,15H2,1-2H3,(H,24,25)/b7-5+,14-12+/t16-,17-,18+,19-,21+/m1/s1
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>
| InChIKey = DLJKPYFALUEJCK-MRVZPHNRBG
 
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
Several recently reported journal articles describing its use as an antiprotozoal include:
| StdInChI = 1S/C21H36O5/c1-3-4-9-13-21(2,26)14-12-17-16(18(22)15-19(17)23)10-7-5-6-8-11-20(24)25/h5,7,12,14,16-19,22-23,26H,3-4,6,8-11,13,15H2,1-2H3,(H,24,25)/b7-5-,14-12+/t16-,17-,18+,19-,21+/m1/s1
 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
* 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>
| StdInChIKey = DLJKPYFALUEJCK-IIELGFQLSA-N
 
}}
* 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>
 
* 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>
 
==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 [[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>
 
==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.<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>
 
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.
 
==Continued use and manufacture around the world==
 
 
{| 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]]
 
 
{{Antiseptics and disinfectants}}
{{Medicated dressings}}
{{Gynecological anti-infectives and antiseptics}}
{{Otologicals}}
 
{{WH}}
{{WS}}

Revision as of 15:17, 4 February 2015

Clioquinol
Error creating thumbnail: File missing
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa600042
Pregnancy
category
  • c
Routes of
administration		Intramuscular
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
E number{{#property:P628}}
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Chemical and physical data
FormulaC21H36O5
Molar mass368.508 g/mol
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)
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