Clioquinol

Structural formula
General
Surname	Clioquinol
other names	5-chloro-7-iodoquinolin-8-ol; Clioquinoline; Chinoform;
Molecular formula	C 9 H 5 ClINO
External identifiers / databases
EC number	204-984-4
ECHA InfoCard	100.004.533
PubChem	2788
ChemSpider	2686
DrugBank	DB04815
Wikidata	Q5134338
Drug information
ATC code	D08 AH30
Drug class	antiseptic
Mechanism of action	Denaturation
properties
Molar mass	305.50 g mol −1
Physical state	firmly
Melting point	178–179 ° C (decomposition)
solubility	4.6 g l −1 at 24 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 301-315-317-319-400
	P: 280-301 + 330 + 331-310-305 + 351 + 338
Toxicological data	400 mg kg −1 ( LD 50 , cat , oral ) ; 69 mg kg −1 ( LD 50 , mouse , oral ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Clioquinol is an antiseptic . It was first patented by Ciba in 1899 . As a cream or ointment, it is used for the external treatment of skin infections caused by bacteria and fungi.

properties

Clioquinol is an almost white, light yellow to light brown powder. It is insoluble in water. It is sparingly soluble in dichloromethane . It must be stored away from light.

It is assumed that the antimicrobial effect of clioquinol is based on the fact that the phenolic hydroxyl group on the C8 atom is able to form chelate complexes with heavy metals . After passing through the bacterial or fungal cell membrane, clioquinol could switch off vital enzymes of the germs by chelating and thereby prevent their growth. If the OH group on the C8 atom is blocked, for example by etherification with alkyl groups, clioquinol is no longer capable of chelating and no longer has an antimicrobial effect. Clioquinol also has an amoebicidal effect.

use

Clioquinol is used for the local treatment of skin infections. The awareness rate is relatively high.

Until the 1970s, clioquinol was used as an oral antiparasitic and to increase intestinal zinc absorption in patients with acrodermatitis enteropathica , a genetic disorder of zinc absorption. Since the oral use of the drug has been found to trigger SMON disease ( subacute myelo -optic neuropathy , subacute myelo-optic neuropathy ), it must no longer be administered orally. From 1953 to 1970, numerous people in Japan suffered nerve damage and paralysis as a result. Oral ingestion can even lead to blindness. Since clioquinol with divalent metals such as calcium - Magnesium - Copper -, and zinc ion forms insoluble complexes, the influence of the drug on is Alzheimer - dementia examined.

synthesis

Clioquinol can be synthesized from 8-hydroxyquinoline by chlorination and subsequent reaction with potassium iodide .

Finished medicinal products

Monopreparations: Linola Sept (D)

Combination preparations

with Flumetason : Locacorten-Vioform (D)
with betamethasone : Betnovate-C (CH)

Individual evidence

↑ ^a ^b ^c ^d ^e ^f ^g Entry on clioquinol. In: Römpp Online . Georg Thieme Verlag, accessed on April 14, 2020.
↑ Entry on clioquinol in the GESTIS substance database of the IFA , accessed on April 15, 2020 (JavaScript required)
↑ ^a ^b Data sheet 5-Chloro-7-iodo-8-quinolinol from Sigma-Aldrich , accessed April 14, 2020 ( PDF ).
↑ Rote Liste ® Service GmbH [Online] : clioquinol . Frankfurt, accessed on April 15, 2020.
↑ European Pharmacopoeia , 6th edition, Deutscher Apotheker Verlag, Stuttgart 2008, ISBN 978-3-7692-3962-1 , pp. 2157-2158.
^ Technical information Linola Sept , Dr. August Wolff, as of April 2016.
^ Harry Auterhoff : Textbook of Pharmaceutical Chemistry , 9th edition 1977, WVG Stuttgart. P. 453.
↑ G. Geisslinger et al .: Mutschler drug effects . 11th edition. WVG, Stuttgart 2019, p. 1126 .
↑ JL Arbiser, S.-K. Kraeft, R. van Leeuwen, SJ Hurwitz, M. Selig, GR Dickersin, A. Flint, H. Randolph Byers, L. Bo Chen: Clioquinol-Zinc Chelate: A Candidate Causative Agent of Subacute Myelo-Optic Neuropathy . In: Molecular Medicine, 1998, Vol. 4, pp. 665-670, doi: 10.1007 / BF03401927 .
↑ D.R., Perez et al .: Clioquinol: To harm or heal . In: Pharmacology & Therapeutics . tape 199 , March 18, 2019, p. 155–164 , doi : 10.1016 / j.pharmthera.2019.03.009 , PMC 6571072 (free full text).
^ A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances [Online] . Thieme, Stuttgart, https://pharmaceutical-substances.thieme.com/ , accessed on April 15, 2020.

[Römpp-1] ↑ ^a ^b ^c ^d ^e ^f ^g Entry on clioquinol. In: Römpp Online . Georg Thieme Verlag, accessed on April 14, 2020.

[Gestis-2] Entry on clioquinol in the GESTIS substance database of the IFA , accessed on April 15, 2020 (JavaScript required)

[Sigma-3] Data sheet 5-Chloro-7-iodo-8-quinolinol from Sigma-Aldrich , accessed April 14, 2020 ( PDF ).

[4] Rote Liste ® Service GmbH [Online] : clioquinol . Frankfurt, accessed on April 15, 2020.

[Europäisches_Arzneibuch-5] European Pharmacopoeia , 6th edition, Deutscher Apotheker Verlag, Stuttgart 2008, ISBN 978-3-7692-3962-1 , pp. 2157-2158.

[6] Technical information Linola Sept , Dr. August Wolff, as of April 2016.

[auterhoff-7] Harry Auterhoff : Textbook of Pharmaceutical Chemistry , 9th edition 1977, WVG Stuttgart. P. 453.

[mutsch-8] G. Geisslinger et al .: Mutschler drug effects . 11th edition. WVG, Stuttgart 2019, p. 1126 .

[9] JL Arbiser, S.-K. Kraeft, R. van Leeuwen, SJ Hurwitz, M. Selig, GR Dickersin, A. Flint, H. Randolph Byers, L. Bo Chen: Clioquinol-Zinc Chelate: A Candidate Causative Agent of Subacute Myelo-Optic Neuropathy . In: Molecular Medicine, 1998, Vol. 4, pp. 665-670, doi: 10.1007 / BF03401927 .

[10] D.R., Perez et al .: Clioquinol: To harm or heal . In: Pharmacology & Therapeutics . tape 199 , March 18, 2019, p. 155–164 , doi : 10.1016 / j.pharmthera.2019.03.009 , PMC 6571072 (free full text).

[Pharmaceutical_Substances-11] A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances [Online] . Thieme, Stuttgart, https://pharmaceutical-substances.thieme.com/ , accessed on April 15, 2020.