Quinacrine 1362163 224828122 2008-07-10T16:27:33Z Lightbot 7178666 Units/dates/other {{Cleanup|date=August 2006}} {{drugbox | IUPAC_name = ''N''<nowiki>'</nowiki>-(6-chloro-2-methoxy-acridin-9-yl)- ''N'', ''N''-diethyl-pentane-1,4-diamine | image = Quinacrine.svg | CAS_number = 83-89-6 | ATC_prefix = | ATC_suffix = | ATC_supplemental = | PubChem = 237 | DrugBank = APRD00317 | C=23 | H=30 | Cl=1 | N=3 | O=1 | molecular_weight = 399.957 g/mol | bioavailability = | protein_bound = 80-90% | metabolism = | elimination_half-life = 5 to 14 days | pregnancy_category = | legal_status = | routes_of_administration = }} '''Quinacrine''' (trade name: '''Atabrine''') is a [[medication|drug]] with a number of different [[medicine|medical]] applications being initially used in the 1930s as an [[antimalarial drug]]. It has also been used as an [[antibiotic]] in the treatment of [[Giardiasis]] (an [[intestinal parasite]])<ref name="pmid17072963">{{cite journal |author=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=}}</ref>, and in research as an inhibitor of [[phospholipase A2]]. It has also been proposed for use in [[systemic lupus erythematosus]].<ref name="pmid16623930">{{cite journal |author=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}}</ref> ==History and licensed uses== Scientists at [[Bayer]] in Germany first synthesised Quinacrine in 1931 and subsequently marketed as Mepacrine or Atebrine. The product was one of the first synthetic substitutes for [[quinine]] although later superseded by [[chloroquine]]. Its mechanism of action against [[giardia]] is uncertain, but it is thought to act against the [[protozoan]]'s cell membrane.<!-- see Drugbank infobox link --> In addition it has been used for treating cutaneous [[leishmaniasis]].<!-- see Drugbank infobox link --> ==Quinacrine sterilization (QS)== Controversially, quinacrine has been used as a method of non-surgical sterilisation. This method <ref>{{cite web | author=Pravin Kini | title=Quinacrine Pellet Method of Female Sterilization | url=http://www.obgyn.net/medical.asp?page=/ENGLISH/PUBS/ARTICLES/kini_art}}</ref>, was developed by Zipper et al who reported a first year failure rate of 3.1%.<ref>{{cite journal | author=Zipper J, Cole LP, Goldsmith A, Wheeler R, Rivera M. | title=Quinacrine hydrochloride pellets: preliminary data on a nonsurgical method of female sterilisation | journal=Asia Oceania J. Obstet. Gynaecol. | year=1980 | volume=18 | pages=275–90 |pmid=6109672}}</ref> [[Pellets]] of quinacrine and an anti-inflammatory drug [[ibuprofen]] are inserted through the cervix into a woman's [[uterus|uterine cavity]] using a preloaded inserter device, similar in manner to [[Intrauterine device|IUCD]] insertion. The procedure is undertaken twice, first in the proliferative phase 6th to 14th of the menstrual cycle and again one month later. The [[sclerosing]] effects of the drugs at the utero-tubal junctions (where the [[Fallopian tubes]] enter the uterus) results in [[scar|scar tissue]] forming over a six week interval to close off the tubes permanently. In over 30,000 cases of quinacrine pellet sterilizations in Vietnam, 10,000 cases in India and 5000 cases in other regions not a single death has been reported;<ref>{{cite journal | author=Sokal, D.C., Kessel. E., Zipper. J., and King. T. | title=Quinacrine: Clinical experience | journal=A background paper for the WHO consultation on the development of new technologies for female sterilization. | year=1994}}</ref> which compares to the fatality rates of surgical sterilizations of 21 per 100,000 in India,<ref>{{cite journal |author=Bhatt RV |title=Camp laparoscopic sterilization deaths in Gujarat State, India, 1978-1980 |journal=Asia-Oceania journal of obstetrics and gynaecology / AOFOG |volume=17 |issue=4 |pages=297–301 |year=1991 |pmid=1839351 |doi=}}</ref> and in the US & UK of respectively 10 & 2 per 100,000.<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}}</ref> ===Controversy about quinacrine sterilization=== {{POV|date=December 2007}} Use of quinacrine for sterilization is highly controversial. The two leading promoters of quinacrine sterilization are Dr. Elton Kessel and Stephen Mumford, who both previously worked for the [[Family Health International]] (FHI), a non-profit agency that funded quinacrine research in [[Chile]] during the 1970s. Subsequent funding from the conservative [[Leland Fikes Foundation]] and the [[Scaife Family Foundation]] made it possible for Mumford and Kessel to provide quinacrine free of charge to researchers, clinicians, and government health agencies worldwide. Mumford and Kessel's gifts of quinacrine were made possible not only through family foundations, but also through the financial support of individuals such as [[Sarah G. Epstein]] and [[Donald Collins]], both board members of the [[Federation for American Immigration Reform]] (FAIR), an organization advocating reduced [[immigration]]. Risks of quinacrine sterilization include [[cancer]], development of abnormal [[lesions]] in the uterus, severe pain, [[ectopic pregnancy]] and fetal exposure.{{Fact|date=September 2007}} The pellets have already been banned in India and Chile (Wall Street Journal, 10/19/98). Quinacrine has never been approved by the [[FDA]] for sterilization. Despite this fact, Kessel and Mumford have solicited [[abortion]] providers in the United States to perform quinacrine sterilization. According to Kessel, official government approval through the FDA would have been "desirable but not necessary" because the FDA permits approved drugs to be used "off-label." The FDA, however, disagreed and in October 1998, it ordered Kessel and Mumford to destroy their existing supply of quinacrine tablets and to immediately stop all export and distribution of the drug. The FDA stated that quinacrine used for sterilizations was an "unapproved new drug and a misbranded drug in violation of the [[Federal Food, Drug, and Cosmetic Act]]." and was an "unsafe use of this drug product.", with the FDA being "very concerned about the safety risks associated with the use of this drug and its effects on women and the fetus if a woman is or becomes pregnant." In addition to forbidding the marketing of quinacrine in the United States for sterilization purposes, the Warning Letter forbade the import of the drug into the United States or its exporting to another country. From September 1998 until December 1999, little was written about Mumford and Kessel's quinacrine plans. The future of quinacrine sterilizations laid in abeyance until [[Warren Buffett]] revived quinacrine research by donating two million dollars to FHI, who will resume animal testing and begin human testing of quinacrine sterilizations in preparation for FDA approval.{{Fact|date=September 2007}} [[Planned Parenthood Federation of America]], the largest reproductive health-care organization in the United States, has defended quinacrine sterilizations, indicating that they are willing to test quinacrine on their patients. In the meantime, [[Jack Lippes]], [[Population Council]] consultant and inventor of the discontinued [[Lippes Loop]] [[IUD]], has received approval from the [[Children's Hospital of Buffalo]] to conduct quinacrine sterilization on ten women.<!-- --><ref>{{cite web | author=Jack Lippes | title=Quinacrine Sterilization (QS) - Safety and Efficacy | url=http://www.quinacrine.com/lippes_for_qs.htm | work=Workshop presentation at the American Public Health Association Annual Meeting, Chicago, IL |date=[[November 8]] [[1999]]}}</ref><!-- --><ref>{{cite journal | author=Judith A.M. Scully | title=Maternal Mortality, Population Control, And The War In Women's Wombs: A Bioethical Analysis Of Quinacrine Sterilizations | journal=Wisconsin International Law Journal | year= | volume=19 | pages=103 | url=http://www.law-lib.utoronto.ca/diana/fulltext/scul.htm}} - Reproduced copy by Women's Human Rights Resources Programme</ref> ====Concerns about consent==== Field tests carried out in [[India]] and [[Vietnam]] led to notable concern over the lack of disclosure to test subjects regarding the permanent effects of the procedure, or that they were given quinacrine at all. In Vietnam, more than a hundred women were given quinacrine during routine pelvic exams, without their knowledge or consent, as "testing." These acts, along with a lack of knowledge about the long-term effects of Quinacrine Sterilization has led to a ban by the [[World Health Organization]] on further human testing.<!-- --><ref>{{cite journal | author=Rao, Mohan | title=Surreptitious Sterilization : A Endangering Process | journal=Health for Millions | month=July-Aug | year=1997 | volume=23 | issue=4 | pages=26–28 | url=http://www.hsph.harvard.edu/grhf-asia/suchana/0110/rao2.html | format={{Dead link|date=May 2008}}}} - Reproduced by Global Reproductive Health Forum South Asia</ref> <!-- not entirely clear if link is to a reproduction of a "Health for Millions" journal article on the GRHFSA's website, or a "Health for Millions" book whose publisher is GRHFSA. --> ==Quinacrine and Creutzfeldt-Jakob disease== Quinacrine has been shown to bind to the [[prion]] protein and prevent the formation of prion aggregates [[in vitro]],<!-- --><ref name="Doh-Ura">{{cite journal | author = 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 | year = 2000 | month=May| pmid = 10775631 | url=http://jvi.asm.org/cgi/content/full/74/10/4894?view=long&pmid=10775631 | doi = 10.1128/JVI.74.10.4894-4897.2000}}</ref> and full clinical trials of its use as a treatment for [[Creutzfeldt-Jakob disease]] are under way in the [[United Kingdom]] and the [[United States]]. Small trials in Japan have reported improvement in the condition of patients with the disease,<!-- --><ref name="Kobayashi">{{cite journal | author = Kobayashi Y, Hirata K, Tanaka H, Yamada T | title = [Quinacrine administration to a patient with Creutzfeldt-Jakob disease who received a cadaveric dura mater graft--an EEG evaluation] | journal = Rinsho Shinkeigaku | volume = 43 | issue = 7 | pages = 403–8 | year = 2003 | month=Jul | pmid = 14582366}}</ref> although other reports have shown no significant effect,<!-- --><ref name="Haik">{{cite journal | author = 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 | year = 2004 | month=[[28 December]] | pmid = 15623716}}</ref> and treatment of [[scrapie]] in [[lab mouse|mice]] and [[sheep]] has also shown no effect.<!-- --><ref name="Barret">{{cite journal | author = 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 | year = 2003 | month=Aug | pmid = 12857915 | url=http://jvi.asm.org/cgi/content/full/77/15/8462?view=long&pmid=12857915 | doi = 10.1128/JVI.77.15.8462-8469.2003}}</ref><!-- --><ref name="Gayrard">{{cite journal | author = 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 an ovine model of scrapie | journal = Br J Pharmacol | volume = 144 | issue = 3 | pages = 386–93 | year = 2005 | month=Feb | pmid = 15655516 | doi = 10.1038/sj.bjp.0706072}} - [http://www.nature.com/bjp/journal/v144/n3/abs/0706072a.html;jsessionid=26ACDAFB57BFF1222031D5379AE51252 Abstract]</ref> ==References== {{Reflist|2}} ==External links== *[http://www.quinacrine.com/ The most extensive online database about quinacrine sterilization.] *[http://www.quinacrine.com/archive/lipp04b.pdf Clinical Trial Results -- FDA Phase I clinical trial of quinacrine sterilization] * Committee On Women, Population, And The Environment - [http://www.cwpe.org/old_website/quinalert.htm Quinacrine Alert Network] * [http://www.clinicaltrials.gov/show/NCT00183092 National Institute on Aging (NIA) trial] * [http://www.ctu.mrc.ac.uk/studies/cjd.asp Medical Research Council PRION-1 trial] [[Category:Antimalarial agents]] [[Category:Chemical contraception]] [[Category:Experimental methods of birth control]] [[de:Mepacrin]] [[fr:Quinacrine]]