Quinacrine
Encyclopedia
Quinacrine is a drug
with a number of different medical
applications. It is related to mefloquine
.
Antiprotozoal use include targeting Giardiasis
, where quinacrine is indicated as a primary agent for patients with metronidazole
-resistant giardiasis and patients who should not receive or can not tolerate metronidazole. Giardiasis that is very resistant may even require a combination of quinacrine and metronidazole.
Quinacrine is also used "off-label" for the treatment of systemic lupus erythematosus
, indicated in the treatment of discoid and subcutaneous lupus erythematosus, particularly in patients unable to take chloroquine
derivatives.
As an intrapleural sclerosing agent, it is used as pneumothorax
prophylaxis in patients at high risk of recurrence, e.g., cystic fibrosis patients.
Quinacrine is not the drug of choice because side effects are common, including toxic psychosis, and may cause permanent damage. View Mefloquine
page for more information.
In addition to medical applications, quinacrine is an effective in vitro research tool for the epifluorescent visualization of cells, especially platelets. Quinacrine is a green fluorescent dye taken up by most cells. Platelet store quinacrine in dense granules.
is uncertain, but it is thought to act against the protozoan's cell membrane.
It is known to act as a histamine N-methyltransferase
inhibitor.
It also inhibits NF-κB and activates p53
.
. This antiprotozoal is also approved for the treatment of Giardiasis
(an intestinal parasite
), and has been researched as an inhibitor of phospholipase A2
.
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although later superseded by chloroquine
.
protein and prevent the formation of prion aggregates in vitro
,
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,
although other reports have shown no significant effect,
and treatment of scrapie
in mice and sheep has also shown no effect. 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 quinacrine.
Pellets
of quinacrine are inserted through the cervix into a woman's uterine cavity
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 sclerosing effects of the drugs at the utero-tubal junctions (where the 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 already undergone Phase I clinical testing for F.D.A. approval. The F.D.A. passed this method during a Phase I clinical trial as showing in a small sample that the method is safe and effective. This was the result of a study published by Dr. Lippes at the SUNY Buffalo (see link below). In addition, the F.D.A. has waived the necessity for Phase II clinical trials because of the extensive data of prior safe use of Quinacine. 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 legally used "off-label" in the US, until final FDA approval of the method is obtained.
Many peer reviewed studies suggest that quinacrine sterilization (QS) is potentially safer than surgical sterilization. Nevertheless, in 1998 the Supreme Court of India banned the import or use of the drug, based on reports that it could cause cancer
or ectopic pregnancies
.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
with a number of different medical
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
applications. It is related to mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
.
Uses
Its main effects are as an antiprotozoal, antirheumatic and an intrapleural sclerosing agent.Antiprotozoal use include targeting Giardiasis
Giardiasis
Giardiasis or beaver fever in humans is a diarrheal infection of the small intestine by a single-celled organism Giardia lamblia. Giardiasis occurs worldwide with a prevalence of 20–30% in developing countries. In the U.S., 20,000 cases are reported to the CDC annually, but the true annual...
, where quinacrine is indicated as a primary agent for patients with metronidazole
Metronidazole
Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....
-resistant giardiasis and patients who should not receive or can not tolerate metronidazole. Giardiasis that is very resistant may even require a combination of quinacrine and metronidazole.
Quinacrine is also used "off-label" for the treatment of systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, indicated in the treatment of discoid and subcutaneous lupus erythematosus, particularly in patients unable to take chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
derivatives.
As an intrapleural sclerosing agent, it is used as pneumothorax
Pneumothorax
Pneumothorax is a collection of air or gas in the pleural cavity of the chest between the lung and the chest wall. It may occur spontaneously in people without chronic lung conditions as well as in those with lung disease , and many pneumothoraces occur after physical trauma to the chest, blast...
prophylaxis in patients at high risk of recurrence, e.g., cystic fibrosis patients.
Quinacrine is not the drug of choice because side effects are common, including toxic psychosis, and may cause permanent damage. View Mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
page for more information.
In addition to medical applications, quinacrine is an effective in vitro research tool for the epifluorescent visualization of cells, especially platelets. Quinacrine is a green fluorescent dye taken up by most cells. Platelet store quinacrine in dense granules.
Mechanism
Its mechanism of action against protozoaProtozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
is uncertain, but it is thought to act against the protozoan's cell membrane.
It is known to act as a histamine N-methyltransferase
Histamine N-methyltransferase
Histamine N-methyltransferase is one of two enzymes involved in the metabolism of histamine. The other being diamine oxidase. Histamine N-methyltransferase catalyzes the methylation of histamine in the presence of S-adenosylmethionine forming N-methylhistamine. HMT is present in most body tissues...
inhibitor.
It also inhibits NF-κB and activates p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
.
Antiprotozoal
Quinacrine was initially approved in the 1930s as an antimalarial drugAntimalarial drug
Antimalarial medications, also known as antimalarials, are designed to prevent or cure malaria. Such drugs may be used for some or all of the following:* Treatment of malaria in individuals with suspected or confirmed infection...
. This antiprotozoal is also approved for the treatment of Giardiasis
Giardiasis
Giardiasis or beaver fever in humans is a diarrheal infection of the small intestine by a single-celled organism Giardia lamblia. Giardiasis occurs worldwide with a prevalence of 20–30% in developing countries. In the U.S., 20,000 cases are reported to the CDC annually, but the true annual...
(an intestinal parasite
Intestinal parasite
Intestinal parasites are parasites that populate the gastro-intestinal tract in humans and other animals. They can live throughout the body, but most prefer the intestinal wall. Means of exposure include: ingestion of undercooked meat, drinking infected water, and skin absorption...
), and has been researched as an inhibitor of phospholipase A2
Phospholipase A2
Phospholipases A2 are enzymes that release fatty acids from the second carbon group of glycerol. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond releasing arachidonic acid and lysophospholipids...
.
Scientists at Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
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
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
although later superseded by chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
.
Creutzfeldt-Jakob disease
Quinacrine has been shown to bind to the prionPrion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
protein and prevent the formation of prion aggregates in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
,
and full clinical trials of its use as a treatment for Creutzfeldt-Jakob disease
Creutzfeldt-Jakob disease
Creutzfeldt–Jakob disease or CJD is a degenerative neurological disorder that is incurable and invariably fatal. CJD is at times called a human form of mad cow disease, given that bovine spongiform encephalopathy is believed to be the cause of variant Creutzfeldt–Jakob disease in humans.CJD...
are under way in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
and the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. 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
Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies , which are related to bovine spongiform encephalopathy and chronic wasting disease of deer. Like other spongiform encephalopathies, scrapie...
in mice and sheep has also shown no effect. 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 quinacrine.
Quinacrine non-surgical sterilization for women (QS)
The use of quinacrine for non-surgical sterilization for women has also been researched. This method, was developed by Zipper et al. who reported a first year failure rate of 3.1%. However, despite a multitude clinical studies on the use of quinacrine and female sterilization, no randomized, controlled trials have been reported to date and there is some controversy over its use.Pellets
Pelletizing
Pelletizing is the process of compressing or molding a material into the shape of a pellet. A wide range of different materials are pelletized including chemicals, iron ore, animal compound feed, and more.- Pelletizing of iron ore :...
of quinacrine are inserted through the cervix into a woman's uterine cavity
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
using a preloaded inserter device, similar in manner to IUCD
Intrauterine device
A copper IUD is a type of intrauterine device. Most IUDs have a plastic T- or U-shaped frame which is wrapped in copper wire, with the exception of Gynefix, which is a plastic string with several copper beads, affixed to the fundus of the uterus...
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 sclerosing effects of the drugs at the utero-tubal junctions (where the Fallopian tubes enter the uterus) results in scar tissue
Scar
Scars are areas of fibrous tissue that replace normal skin after injury. A scar results from the biological process of wound repair in the skin and other tissues of the body. Thus, scarring is a natural part of the healing process. With the exception of very minor lesions, every wound results in...
forming over a six week interval to close off the tubes permanently.
In the United States, this method has already undergone Phase I clinical testing for F.D.A. approval. The F.D.A. passed this method during a Phase I clinical trial as showing in a small sample that the method is safe and effective. This was the result of a study published by Dr. Lippes at the SUNY Buffalo (see link below). In addition, the F.D.A. has waived the necessity for Phase II clinical trials because of the extensive data of prior safe use of Quinacine. 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 legally used "off-label" in the US, until final FDA approval of the method is obtained.
Many peer reviewed studies suggest that quinacrine sterilization (QS) is potentially safer than surgical sterilization. Nevertheless, in 1998 the Supreme Court of India banned the import or use of the drug, based on reports that it could cause cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
or ectopic pregnancies
Ectopic pregnancy
An ectopic pregnancy, or eccysis , is a complication of pregnancy in which the embryo implants outside the uterine cavity. With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are dangerous for the parent, since internal haemorrhage is a life threatening complication...
.