Quinacrine

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Quinacrine
Systematic (IUPAC) name
N'-(6-chloro-2-methoxy-acridin-9-yl)- N, N-diethyl-pentane-1,4-diamine
Identifiers
CAS number	83-89-6
ATC code	?
PubChem	237
DrugBank	APRD00317
Chemical data
Formula	C23H30ClN3O
Mol. mass	399.957 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	80-90%
Metabolism	?
Half life	5 to 14 days
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Quinacrine (trade name: Atabrine) is a drug with a number of different medical applications.

As an antimalarial drug, it has been available since the 1930s, but it is currently used as an antibiotic in the treatment of Giardiasis, an intestinal parasite. Extended consumption of quinacrine is also linked to a yellowing of the epidermis in a fashion similar to, and easily mistaken for, jaundice.

Contents 1 History 2 Quinacrine sterilization (QS) 2.1 Field tests 3 Quinacrine and Creutzfeldt-Jakob disease 4 Footnotes 5 External links

[edit] History

Scientists at Bayer in Germany first synthesised Quinacrine in 1931. The product was one of the first synthetic substitutes for quinine. The product was subsequently marketed as Mepacrine or Atebrin while Quinacrine was its American name.

[edit] Quinacrine sterilization (QS)

Quinacrine pellets, inserted in a woman's uterine cavity, can result in permanent sterilization, but do not always prevent pregnancy. The quinacrine acts as a sclerosing agent, and chemically burns surface tissue at the utero-tubal junctions, where the Fallopian tubes enter the uterus. In six weeks scar tissue forms, closing off the tubes permanently. Use of quinacrine for sterilization is highly controversial.

The two leading promoters of quinacrine sterilization are Dr. Elton Kessel and Stephen Mumford. Kessel is a Harvard and University of Chicago trained medical doctor and former director of Family Health International (FHI), a non-profit agency that funded quinacrine research in Chile during the 1970s, under Pinochet, who had US support. His partner, Stephen Mumford, was also an employee of FHI. Mumford was dismissed for writing a string of articles blaming the Vatican for the United States' failure to adopt a policy classifying population growth in the Third World as a threat to the national security of the United States.

Private funding from the right-wing Leland Fikes Foundation and the Scaife Family Foundation have 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 are made possible not only through right-wing 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), a conservative, anti-immigrant organization. Regarding immigrants and population, Mr. Mumford has said, "This explosion in human numbers, which after 2050 will come entirely from immigrants and the offspring of immigrants, will dominate our lives. There will be chaos and anarchy."(The Wall Street Journal, June 1998)

Risks of quinacrine sterilization include cancer, development of abnormal lesions in the uterus, severe pain, ectopic pregnancy and fetal exposure. Quinacrine has also caused deaths. 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." Kessel argues that since quinacrine is an approved drug for treating malaria, doctors should be free to prescribe quinacrine for any purpose, including sterilization. Thus, Mumford concludes that it is "legal for clinicians to perform this procedure on American women as an off-label use of an approved drug."

The FDA, however, disagreed. 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." It also indicated that quinacrine pellets used for non-surgical female sterilizations was an "unsafe use of this drug product." Finally, the FDA stated that it was "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."

The FDA warned Kessel and Mumford that if they did not "immediately halt" distribution of the quinacrine pellets, they could face possible seizure of the pellets or criminal prosecution. 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 under sections 301(a) and (d) of the Food, Drug, and Cosmetic Act (FDCA). The FDA also warned Dr. Mumford that under section 801, a product may only be exported to another country if it complies with the laws of that country and has valid marketing authorization by the appropriate authority. The letter concluded that since quinacrine is not approved for use in non-surgical sterilizations in any country listed under the Act, exporting the drug--at all--would violate the Act.

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 Buffet, the self-made billionaire investment guru, revived quinacrine research by donating two million dollars to FHI. With this two million dollar donation, FHI will resume animal testing and begin human testing of quinacrine sterilizations in preparation for FDA approval. 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.^[1][2]

[edit] Field tests

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.^[3]

[edit] Quinacrine and Creutzfeldt-Jakob disease

Quinacrine has been shown to bind to the prion protein and prevent the formation of prion aggregates in vitro,^[4] 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,^[5] although other reports have shown no significant effect,^[6] and treatment of scrapie in mice and sheep has also shown no effect.^[7][8]

[edit] Footnotes

[edit] External links

• Committee On Women, Population, And The Environment - Quinacrine Alert Network
• National Institute on Aging (NIA) trial
• Medical Research Council PRION-1 trial
• Contraception Resource Center from the Association of Reproductive Health Professionals.