Mepacrine

Source: Wikipedia, the free encyclopedia.
Mepacrine
QP51AX04 (WHO)
Pharmacokinetic data
Protein binding80–90%
Elimination half-life5–14 days
Identifiers
  • (RS)-N′-(6-Chloro-2-methoxy-acridin-9-yl)-N,N-diethylpentane-1,4-diamine
JSmol)
  • CCN(CC)CCCC(C)Nc1c2ccc(cc2nc3c1cc(cc3)OC)Cl
  • InChI=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) checkY
  • Key:GPKJTRJOBQGKQK-UHFFFAOYSA-N checkY
  (verify)

Mepacrine, also called quinacrine or by the trade names Atabrine or Atebrin (german), is a medication with several uses. It is related to

compounding pharmacies, as of August 2020 it is unavailable in the United States.[1]

Medical uses

Papua New Guinea during World War II

The main uses of mepacrine are as an

sclerosing agent.[2]

Antiprotozoal use include targeting giardiasis, where mepacrine is indicated as a primary agent for patients with metronidazole-resistant giardiasis and patients who should not receive or cannot tolerate metronidazole. Giardiasis that is very resistant may even require a combination of mepacrine and metronidazole.[2]

Mepacrine is also used off-label for the treatment of

systemic lupus erythematosus,[3] indicated in the treatment of discoid and subcutaneous lupus erythematosus, particularly in patients unable to take chloroquine derivatives.[2]

As an intrapleural sclerosing agent, it is used as pneumothorax prophylaxis in patients at high risk of recurrence, e.g., cystic fibrosis patients.[2]

Mepacrine is not the drug of choice because side effects are common, including toxic psychosis, and may cause permanent damage. See mefloquine for more information.

In addition to medical applications, mepacrine is an effective in vitro research tool for the epifluorescent visualization of cells, especially platelets. Mepacrine is a green fluorescent dye taken up by most cells. Platelets store mepacrine in dense granules.[4]

Mechanism

Its mechanism of action against

protozoan
's cell membrane. It is known to act as a histamine N-methyltransferase inhibitor. It also inhibits NF-κB and activates p53.

History

Antiprotozoal

Atabrine and mosquito poster

Mepacrine was initially approved in the 1930s as an

second World War by Allied forces fighting in North Africa and the Far East to prevent malaria.[5]

This

intestinal parasite),[6] and has been researched as an inhibitor of phospholipase A2
.

Scientists at Bayer in Germany first synthesised mepacrine in 1931. The product was one of the first synthetic substitutes for quinine although later superseded by chloroquine.

Anthelmintics

In addition it has been used for treating

tapeworm infections.[7]

Creutzfeldt–Jakob disease

Mepacrine has been shown to bind to the prion protein and prevent the formation of prion aggregates in vitro,[8] 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,[9] although other reports have shown no significant effect,[10] and treatment of

mice and sheep has also shown no effect.[11][12] 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.[13]

Non-surgical sterilization for women

The use of mepacrine for non-surgical sterilization for women has also been studied. The first report of this method claimed a first year failure rate of 3.1%.[14] 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.[2]

Fallopian tubes enter the uterus) results in scar tissue
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 off-label.

Many peer reviewed studies suggest that

surgical sterilization.[16][17] Nevertheless, in 1998 the Supreme Court of India banned the import or use of the drug, allegedly based on reports that it could cause cancer or ectopic pregnancies.[18]

Skin dye

During the Second Sino-Japanese War, American Sino-American Cooperative Organization operatives yellowed their skin using mepacrine tablets in order to more closely match the skin color of their Chinese peers.[19]

See also

References

  1. ^ "Quinacrine Shortage & What the ACR Is Doing about It". 13 March 2019 [8 February 2019]. Retrieved 24 August 2020.
  2. ^ a b c d e Drugs.com: Quinacrine. Retrieved on August 24, 2009.
  3. PMID 16623930
    .
  4. S2CID 24132625
    .
  5. PMID 21383088
    .
  6. PMID 17072963
    .
  7. ^ "quinacrine" at Dorland's Medical Dictionary
  8. PMID 10775631
    .
  9. PMID 14582366
    .
  10. S2CID 37534686
    .
  11. PMID 12857915
    .
  12. PMID 15655516
    . - Abstract
  13. PMID 19956709
    .
  14. S2CID 41946631
    .
  15. PMID 14763179
    .
  16. ^ Sokal, D.C., Kessel. E., Zipper. J., and King. T. (1994). "Quinacrine: Clinical experience". Background Paper for the World Health Organization Consultation on the Development of New Technologies for Female Sterilization: 25–7.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. S2CID 15179539.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  18. ^ George, Nirmala (July 25, 1998). "Govt drags feet on quinacrine threat". Indian Express..
  19. ^ "How naked World War II sailors ended up riding Mongolian ponies in the Gobi Desert to shoot bazookas at the Japanese". 2019-01-26.

External links

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