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| Trade names | Atabrine, Atebrin |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
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| Pharmacokinetic data | |
| Protein binding | 80–90% |
| Eliminationhalf-life | 5–14 days |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.001.371 |
| Chemical and physical data | |
| Formula | C23H30ClN3O |
| Molar mass | 399.96 g·mol−1 |
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Mepacrine, also calledquinacrine or by the trade namesAtabrine orAtebrin, is a medication with several uses. It is related tochloroquine andmefloquine. Although available fromcompounding pharmacies, as of August 2020 approved formulations are not available in the United States.[1]
The main uses of mepacrine are as anantiprotozoal,antirheumatic, and an intrapleuralsclerosing agent.[2]
Mepacrine findsoff-label use as a primary antimicrobial agent for patients withmetronidazole-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.[2]
Mepacrine is also used off-label for the treatment ofsystemic lupus erythematosus,[3] indicated in the treatment ofdiscoid and subcutaneous lupus manifestations, particularly in patients who are unable to takehydroxychloroquine.[2]
As ansclerosing agent, it is used aspneumothorax prophylaxis in patients at high risk of recurrence, e.g., in those with cystic fibrosis.[2]
Mepacrine is not the drug of choice because side effects are common, includingtoxic psychosis, and may cause permanent damage. Seemefloquine for more information.
In addition to medical applications, mepacrine is an effective in vitro research tool for theepifluorescent visualization of cells, especially platelets. Mepacrine is a green fluorescent dye taken up by most cells. Platelets store mepacrine in dense granules.[4]
Its mechanism of action againstprotozoa is uncertain, but it is thought to act against theprotozoan's cell membrane.It is known to act as ahistamineN-methyltransferase inhibitor.It also inhibitsNF-κB and activatesp53.
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Mepacrine was initially approved in the 1930s as anantimalarial drug. It was used extensively during thesecond World War by Allied forces fighting in North Africa and the Far East to prevent malaria.[5]
Thisantiprotozoal is also approved[where?][by whom?] for the treatment ofgiardiasis (anintestinal parasite),[6] and has been researched as an inhibitor ofphospholipase A2.
Scientists atBayer in Germany first synthesised mepacrine in 1931. The product was one of the first synthetic substitutes forquinine although later superseded bychloroquine.
In addition it has been used for treatingtapeworm infections.[7]
Mepacrine has been shown to bind to theprion protein and prevent the formation of prion aggregatesin vitro,[8]and full clinical trials of its use as a treatment forCreutzfeldt–Jakob disease are under way in theUnited Kingdom and theUnited 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 ofscrapie inmice andsheep has also shown no effect.[11][12] Possible reasons for the lack of anin 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]
The use of mepacrine for non-surgicalsterilization 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]
Pellets of mepacrine are inserted through the cervix into a woman'suterine cavity using a preloaded inserter device, similar in manner toIUCD 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. Thesclerosing effects of the drugs at the utero-tubal junctions (where theFallopian tubes enter the uterus) results inscar 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 usedoff-label.
Many peer reviewed studies suggest that[15] mepacrine sterilization (QS) is potentially safer thansurgical 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 causecancer orectopic pregnancies.[18]
During World War II, Caucasian American operatives involved inSino-American Cooperative Organization activities theSecond Sino-Japanese War yellowed their skin using mepacrine tablets in order better blend in with the native Chinese population.[19]
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