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Revision as of 12:18, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456988297 of page Quinacrine for the Chem/Drugbox validation project (updated: 'DrugBank').		Latest revision as of 16:10, 24 December 2024 edit Alex Nico (talk | contribs)Extended confirmed users959 edits →Medical uses
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			{{Short description|Medication}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{MCN|date=August 2024}}
	{{Drugbox		{{Drugbox
		⚫	| verifiedrevid = 464378394
	| Verifiedfields = changed
		⚫	| IUPAC_name = (''RS'')-''N''′-(6-Chloro-2-methoxy-acridin-9-yl)-''N'',''N''-diethylpentane-1,4-diamine
⚫	| verifiedrevid = 409764873
⚫	| IUPAC_name = (''RS'')-''N''<nowiki>'</nowiki>-(6-chloro-2-methoxy-acridin-9-yl)- ''N'', ''N''-diethyl-pentane-1,4-diamine
	| image = Quinacrine.svg		| image = Quinacrine.svg
	| width = 200		| width = 215
	| imagename = 1 : 1 mixture (racemate)
	| drug_name = Quinacrine
	<!--Clinical data-->		<!--Clinical data-->
	| tradename = Atabrine		| tradename = Atabrine, Atebrin
	| Drugs.com = {{drugs.com|CONS|quinacrine}}		| Drugs.com = {{drugs.com|CONS|quinacrine}}
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| protein_bound = 80-90%		| protein_bound = 80–90%
	| elimination_half-life = 5 to 14 days		| elimination_half-life = 5–14 days
	<!--Identifiers-->		<!--Identifiers-->
⚫	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 83-89-6		| CAS_number = 83-89-6
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	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = H0C805XYDE		| UNII = H0C805XYDE
			| KEGG = D08179
	| ChEBI_Ref = {{ebicite|changed|EBI}}
		⚫	| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 8711		| ChEBI = 8711
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 7568		| ChEMBL = 7568
			| PDB_ligand = QUN
	<!--Chemical data-->		<!--Chemical data-->
	| C=23 | H=30 | Cl=1 | N=3 | O=1		| C=23 | H=30 | Cl=1 | N=3 | O=1
	| molecular_weight = 399.957 g/mol
	| smiles = CCN(CC)CCCC(C)Nc1c2ccc(cc2nc3c1cc(cc3)OC)Cl		| smiles = CCN(CC)CCCC(C)Nc1c2ccc(cc2nc3c1cc(cc3)OC)Cl
	| InChI = 1/C23H30ClN3O/c1-5-27(6-2)13-7-8-16(3)25-23-19-11-9-17(24)14-22(19)26-21-12-10-18(28-4)15-20(21)23/h9-12,14-16H,5-8,13H2,1-4H3,(H,25,26)
	| InChIKey = GPKJTRJOBQGKQK-UHFFFAOYAJ
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C23H30ClN3O/c1-5-27(6-2)13-7-8-16(3)25-23-19-11-9-17(24)14-22(19)26-21-12-10-18(28-4)15-20(21)23/h9-12,14-16H,5-8,13H2,1-4H3,(H,25,26)		| StdInChI = 1S/C23H30ClN3O/c1-5-27(6-2)13-7-8-16(3)25-23-19-11-9-17(24)14-22(19)26-21-12-10-18(28-4)15-20(21)23/h9-12,14-16H,5-8,13H2,1-4H3,(H,25,26)
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	| StdInChIKey = GPKJTRJOBQGKQK-UHFFFAOYSA-N		| StdInChIKey = GPKJTRJOBQGKQK-UHFFFAOYSA-N
	}}		}}
			'''Mepacrine''', also called '''quinacrine''' or by the trade names '''Atabrine''' or '''Atebrin''', is a medication with several uses. It is related to ] and ]. Although available from ], as of August 2020 approved formulations are not available in the United States.<ref>{{Cite web|orig-year=8 February 2019 |date= 13 March 2019|title=Quinacrine Shortage & What the ACR Is Doing about It|url=https://www.the-rheumatologist.org/article/quinacrine-shortage-what-the-acr-is-doing-about-it/|access-date=24 August 2020}}</ref>
			==Medical uses==
			]); this sign was posted at the 363rd Station Hospital on ]]]
			The main uses of mepacrine are as an ], ], and an intrapleural ] agent.<ref name=drugsdotcom> Retrieved on August 24, 2009.</ref>
			Mepacrine is used off label as a primary antimicrobial agent for patients with ]-resistant giardiasis and patients who should not receive or cannot tolerate metronidazole. Giardiasis with a high level of drug resistance may even require a combination of mepacrine and metronidazole to cure.<ref name=drugsdotcom/>
			Mepacrine is also used off-label for the treatment of ],<ref name="pmid16623930">{{cite journal |vauthors=Toubi E, Kessel A, Rosner I, Rozenbaum M, Paran D, Shoenfeld Y |title=The reduction of serum B-lymphocyte activating factor levels following quinacrine add-on therapy in systemic lupus erythematosus |journal=Scand. J. Immunol. |volume=63 |issue=4 |pages=299–303 |year=2006 |pmid=16623930 |doi=10.1111/j.1365-3083.2006.01737.x|doi-access=free }}</ref> indicated in the treatment of ] and subcutaneous lupus manifestations, particularly in patients who are unable to take ].<ref name=drugsdotcom/>
			As an ], it is used as ] prophylaxis in patients at high risk of recurrence, e.g., in those with cystic fibrosis.<ref name=drugsdotcom/>
			Mepacrine is not the drug of choice because side effects are common, including ], and may cause permanent damage. See ] for more information.
			In addition to medical applications, mepacrine is an effective in vitro research tool for the ] visualization of cells, especially platelets. Mepacrine is a green fluorescent dye taken up by most cells. Platelets store mepacrine in dense granules.<ref>{{cite journal |vauthors=Wall JE, Buijs-Wilts M, Arnold JT, etal | title = A flow cytometric assay using mepacrine for study of uptake and release of platelet dense granule contents. | journal = Br. J. Haematol. | volume = 89 | issue = 2 | pages = 380–385 | year = 1995 | doi = 10.1111/j.1365-2141.1995.tb03315.x| pmid = 7873389 | s2cid = 24132625 }}</ref>
			==Mechanism==
			Its mechanism of action against ] is uncertain, but it is thought to act against the ]'s cell membrane.
			It is known to act as a ] inhibitor.
			It also inhibits ] and activates ].
			==History==
			===Antiprotozoal===
			]
			Mepacrine was initially approved in the 1930s as an ]. It was used extensively during the ] by Allied forces fighting in North Africa and the Far East to prevent malaria.<ref>{{cite journal | author = Baird JK | title = Resistance to chloroquine unhinges vivax malaria therapeutics. | journal = Antimicrob. Agents Chemother. | year = 2011 | volume = 55 | issue = 5 | pages = 1827–1830 | doi=10.1128/aac.01296-10 | pmid=21383088 | pmc=3088196}}</ref>
			This ] is also approved{{where|date=December 2024}}{{by whom|date=December 2024}} for the treatment of ] (an ]),<ref name="pmid17072963">{{cite journal |vauthors=Canete R, Escobedo AA, Gonzalez ME, Almirall P |title=Randomized clinical study of five days apostrophe therapy with mebendazole compared to quinacrine in the treatment of symptomatic giardiasis in children |journal=World J. Gastroenterol. |volume=12 |issue=39 |pages=6366–70 |year=2006 |pmid=17072963 |doi=10.3748/wjg.v12.i39.6366|pmc=4088148 |doi-access=free }}</ref> and has been researched as an inhibitor of ].
			Scientists at ] in Germany first synthesised mepacrine in 1931. The product was one of the first synthetic substitutes for ] although later superseded by ].
			===Anthelmintics===
			In addition it has been used for treating ] infections.<ref>{{DorlandsDict|nine/000956295|quinacrine}}</ref>
			===Creutzfeldt–Jakob disease===
			Mepacrine has been shown to bind to the ] protein and prevent the formation of prion aggregates '']'',<ref name="Doh-Ura">{{cite journal |vauthors=Doh-Ura K, Iwaki T, Caughey B | title = Lysosomotropic Agents and Cysteine Protease Inhibitors Inhibit Scrapie-Associated Prion Protein Accumulation | journal = J Virol | volume = 74 | issue = 10 | pages = 4894–7 |date=May 2000| pmid = 10775631 | doi = 10.1128/JVI.74.10.4894-4897.2000 | pmc = 112015}}</ref>
			and full clinical trials of its use as a treatment for ] are under way in the ] and the ]. Small trials in Japan have reported improvement in the condition of patients with the disease,<ref name="Kobayashi">{{cite journal |vauthors=Kobayashi Y, Hirata K, Tanaka H, Yamada T | title = | journal = Rinsho Shinkeigaku | volume = 43 | issue = 7 | pages = 403–8 |date=July 2003 | pmid = 14582366}}</ref>
			although other reports have shown no significant effect,<ref name="Haik">{{cite journal |vauthors=Haïk S, Brandel J, Salomon D, Sazdovitch V, Delasnerie-Lauprêtre N, Laplanche J, Faucheux B, Soubrié C, Boher E, Belorgey C, Hauw J, Alpérovitch A | title = Compassionate use of quinacrine in Creutzfeldt–Jakob disease fails to show significant effects | journal = Neurology | volume = 63 | issue = 12 | pages = 2413–5 |date=28 December 2004 | pmid = 15623716 | doi=10.1212/01.wnl.0000148596.15681.4d| s2cid = 37534686 }}</ref>
			and treatment of ] in ] and ] has also shown no effect.<ref name="Barret">{{cite journal |vauthors=Barret A, Tagliavini F, Forloni G, Bate C, Salmona M, Colombo L, De Luigi A, Limido L, Suardi S, Rossi G, Auvré F, Adjou K, Salès N, Williams A, Lasmézas C, Deslys J | title = Evaluation of Quinacrine Treatment for Prion Diseases | journal = J. Virol. | volume = 77 | issue = 15 | pages = 8462–9 |date=August 2003 | pmid = 12857915 | doi = 10.1128/JVI.77.15.8462-8469.2003 | pmc = 165262}}</ref><ref name="Gayrard">{{cite journal |vauthors=Gayrard V, Picard-Hagen N, Viguié C, Laroute V, Andréoletti O, Toutain P | title = A possible pharmacological explanation for quinacrine failure to treat prion diseases: pharmacokinetic investigations in a ovine model of scrapie | journal = Br. J. Pharmacol. | volume = 144 | issue = 3 | pages = 386–93 |date=February 2005 | pmid = 15655516 | doi = 10.1038/sj.bjp.0706072 | pmc = 1576015}} -
			</ref> Possible reasons for the lack of an ''in vivo effect'' include inefficient penetration of the blood–brain barrier, as well as the existence of drug-resistant prion proteins that increase in number when selected for by treatment with mepacrine.<ref name="Ghaemmaghami">{{cite journal |vauthors=Ghaemmaghami S, Ahn M, Lessard P, Giles K, Legname G, etal | title = Continuous Quinacrine Treatment Results in the Formation of Drug-Resistant Prions | journal = PLOS Pathogens | volume = 5 | issue = 11 | pages = 2413–5 |date=November 2009 | doi = 10.1371/journal.ppat.1000673 | pmid = 19956709 | pmc = 2777304 | editor1-last = Mabbott | editor1-first = Neil | doi-access = free }}</ref>
			===Non-surgical sterilization for women===
			The use of mepacrine for non-surgical ] for women has also been studied. The first report of this method claimed a first year failure rate of 3.1%.<ref>{{cite journal |vauthors=Zipper J, Cole LP, Goldsmith A, Wheeler R, Rivera M | title=Quinacrine hydrochloride pellets: preliminary data on a nonsurgical method of female sterilisation | journal=International Journal of Gynecology & Obstetrics | year=1980 | volume=18 | pages=275–90 |pmid=6109672 | issue=4| doi=10.1002/j.1879-3479.1980.tb00496.x | s2cid=41946631 }}</ref> However, despite a multitude of clinical studies on the use of mepacrine and female sterilization, no randomized, controlled trials have been reported to date and there is some controversy over its use.<ref name=drugsdotcom/>
			] of mepacrine are inserted through the cervix into a woman's ] using a preloaded inserter device, similar in manner to ] insertion. The procedure is undertaken twice, first in the proliferative phase, 6 to 12 days following the first day of the menstrual cycle and again one month later. The ] effects of the drugs at the utero-tubal junctions (where the ] enter the uterus) results in ] forming over a six-week interval to close off the tubes permanently.
			In the United States, this method has undergone Phase I clinical testing. The FDA has waived the necessity for Phase II clinical trials because of the extensive data pertaining to other uses of mepacrine. The next step in the FDA approval process in the United States is a Phase III large multi-center clinical trial. The method is currently used ].
			Many peer reviewed studies suggest that<ref>{{cite journal|title=Quinacrine sterilization: reports on 40,252 cases.|journal=International Journal of Gynaecology and Obstetrics |date=October 2003|volume=83 |issue=Suppl 2|pages=S1–159|pmid=14763179}}</ref> mepacrine sterilization (QS) is potentially safer than ].<ref>{{cite journal | author=Sokal, D.C., Kessel. E., Zipper. J., and King. T. | title=Quinacrine: Clinical experience | journal=Background Paper for the World Health Organization Consultation on the Development of New Technologies for Female Sterilization | year=1994 |pages=25–7}}</ref><ref>{{cite journal | author=Peterson, H.B., Lubell, L., DeStefano, F., and Ory, H.W.| title=The safety and efficacy of tubal sterilization: an international overview | journal=Int. J. Gynaecol. Obstet. | year=1983 | pages=139–44 |pmid=6136433| doi=10.1016/0020-7292(83)90051-6| volume=21 | issue=2| s2cid=15179539 }}</ref> Nevertheless, in 1998 the Supreme Court of India banned the import or use of the drug, allegedly based on reports that it could cause ] or ].<ref>{{Cite journal|title=Govt drags feet on quinacrine threat|first=Nirmala|last=George|journal=Indian Express|date=July 25, 1998|url=http://www.indianexpress.com/res/web/pIe/ie/daily/19980725/20650684.html}}.</ref>
			===Skin dye===
			During World War II, Caucasian American operatives involved in ] activities the ] yellowed their skin using mepacrine tablets in order better blend in with the native Chinese population.<ref name="NavyTimes">{{Cite web | url=https://www.navytimes.com/news/your-navy/2018/12/30/how-naked-world-war-ii-sailors-ended-up-riding-mongolian-ponies-in-the-gobi-desert-to-shoot-bazookas-at-the-japanese/ | title=How naked World War II sailors ended up riding Mongolian ponies in the Gobi Desert to shoot bazookas at the Japanese| date=2019-01-26}}</ref>
			==See also==
			* ]
			* ]
			* ]
			* ]
			==References==
			{{Reflist|2}}
			==External links==
			*
			{{Antiprotozoal agent}}
			{{Excavata antiparasitics}}
			{{Anthelmintics}}
			{{Monoamine metabolism modulators}}
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