Mepacrine, also called quinacrine or by the trade name Atabrine, is a medication with several uses. It is related to

chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...

and

mefloquine Mefloquine, sold under the brand name Lariam among others, is a medication used to prevent or treat malaria. When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure. It ...

. Although formerly available from compounding pharmacies, as of August 2020 it is unavailable in the United States.

Medical uses

Atabrine advertisement in Guinea during WW2

The main uses of mepacrine are as an

antiprotozoal Antiprotozoal agents ( ATC code: ATC P01) is a class of pharmaceuticals used in treatment of protozoan infection. A paraphyletic group, protozoans have little in common with each other. For example, ''Entamoeba histolytica'', a unikont eukar ...

, antirheumatic, and an intrapleural

sclerosing Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations ( vascular malformations) and also malformations of the lymphatic system. A medicine is injected into the vessels, w ...

agent.Drugs.com: Quinacrine.
Retrieved on August 24, 2009. Antiprotozoal use include targeting giardiasis, where mepacrine is indicated as a primary agent for patients with

metronidazole Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is ...

-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. Mepacrine is also used off-label for the treatment of

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...

, indicated in the treatment of discoid and subcutaneous lupus erythematosus, particularly in patients unable to take

derivatives. As an intrapleural sclerosing agent, it is used as

pneumothorax A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve i ...

prophylaxis in patients at high risk of recurrence, e.g., cystic fibrosis patients. Mepacrine is not the drug of choice because side effects are common, including

toxic psychosis Substance-induced psychosis (commonly known as toxic psychosis or drug-induced psychosis) is a form of psychosis that is attributed to substance use. It is a psychosis that results from the effects of chemicals or drugs, including those produced b ...

, and may cause permanent damage. See

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.

Mechanism

Its mechanism of action against

protozoa Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...

is uncertain, but it is thought to act against the

protozoan Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...

's cell membrane. It is known to act as a histamine ''N''-methyltransferase inhibitor. It also inhibits

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

and activates

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

History

Antiprotozoal

Mepacrine was initially approved in the 1930s as an

antimalarial drug Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...

. It was used extensively during the

second World War World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposi ...

by Allied forces fighting in North Africa and the Far East to prevent malaria. This

is also approved for the treatment of giardiasis (an

intestinal parasite An intestinal parasite infection is a condition in which a parasite infects the gastro-intestinal tract of humans and other animals. Such parasites can live anywhere in the body, but most prefer the intestinal wall. Routes of exposure and inf ...

), and has been researched as an inhibitor of

phospholipase A2 The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyse the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glyc ...

. Scientists at

Bayer Bayer AG (, commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and one of the largest pharmaceutical companies in the world. Headquartered in Leverkusen, Bayer's areas of business include pharmaceutic ...

in Germany first synthesised mepacrine in 1931. The product was one of the first synthetic substitutes for

quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to '' Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg ...

although later superseded by

Anthelmintics

In addition it has been used for treating

tapeworm Eucestoda, commonly referred to as tapeworms, is the larger of the two subclasses of flatworms in the class Cestoda (the other subclass is Cestodaria). Larvae have six posterior hooks on the scolex (head), in contrast to the ten-hooked Cesto ...

infections.

Creutzfeldt–Jakob disease

Mepacrine has been shown to bind to the

prion Prions are misfolded proteins that have the ability to transmit their misfolded shape onto normal variants of the same protein. They characterize several fatal and transmissible neurodegenerative diseases in humans and many other animals. It i ...

protein and prevent the formation of prion aggregates ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...

'', and full clinical trials of its use as a treatment for

Creutzfeldt–Jakob disease Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes ...

are under way in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and ...

and the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

. Small trials in Japan have reported improvement in the condition of patients with the disease, although other reports have shown no significant effect, and treatment of

scrapie Scrapie () is a fatal, degenerative disease affecting the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies (TSEs), and as such it is thought to be caused by a prion. Scrapie has been known since ...

mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...

and

sheep Sheep or domestic sheep (''Ovis aries'') are domesticated, ruminant mammals typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus '' Ovis'', in everyday usage it almost always refers to domesticate ...

has also shown no effect.
Abstract
/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.

Non-surgical sterilization for women

The use of mepacrine for non-surgical

sterilization Sterilization may refer to: * Sterilization (microbiology), killing or inactivation of micro-organisms * Soil steam sterilization, a farming technique that sterilizes soil with steam in open fields or greenhouses * Sterilization (medicine) rende ...

for women has also been studied. The first report of this method claimed a first year failure rate of 3.1%. 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. Pellets of mepacrine are inserted through the cervix into a woman's

uterine cavity The uterine cavity is the inside of the uterus. It is triangular in shape, the base (broadest part) being formed by the internal surface of the body of the uterus between the openings of the fallopian tubes The fallopian tubes, also known as ...

using a preloaded inserter device, similar in manner to IUCD 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

Fallopian tubes The fallopian tubes, also known as uterine tubes, oviducts or salpinges (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In ot ...

enter the uterus) results in

scar tissue Scar tissue may refer to: Medicine * Scar, an area of fibrous tissue that replaces normal skin after injury * Granulation tissue, a product of healing in major wounds Film and television * ''Scar Tissue'' (1975 film), or ''Wanted: Babysitter'' ...

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 Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...

. Many peer reviewed studies suggest that mepacrine sterilization (QS) is potentially safer than surgical sterilization. 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 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

ectopic pregnancies Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms ...

Skin dye

During the

Second Sino-Japanese War The Second Sino-Japanese War (1937–1945) or War of Resistance (Chinese term) was a military conflict that was primarily waged between the Republic of China and the Empire of Japan. The war made up the Chinese theater of the wider Pacific T ...

, 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.

References

External links

National Institute on Aging (NIA) trial
{{Monoamine metabolism modulators Disulfiram-like drugs Antiprotozoal agents Antimalarial agents Sterilization (medicine) Experimental methods of birth control Acridines Chloroarenes Phenol ethers Aromatic amines Diethylamino compounds