Quinacrine

Quinacrine

Systematic (IUPAC) name
(RS)-N'-(6-chloro-2-methoxy-acridin-9-yl)- N, N-diethyl-pentane-1,4-diamine
Identifiers
CAS number	83-89-6
ATC code	P01AX05 QP51AX04
PubChem	237
DrugBank	APRD00317
ChemSpider	232
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	?
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Quinacrine (trade name Atabrine) is a drug with a number of different medical applications.

Uses

Its main effects are as an antiprotozoal, antirheumatic and an intrapleural sclerosing agentl.^[1]

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.^[1]

Quinacrine is also used "off-label" for the treatment of systemic lupus erythematosus,^[2] indicated in the treatment of discoid and subcutaneous lupus erythematosus, particularly in patients unable to take chloroquine derivatives.^[1]

As an intrapleural sclerosing agent, it is used as pneumothorax prophylaxis in patients at high risk of recurrence, e.g., cystic fibrosis patients.^[1]

Mechanism

Its mechanism of action against protozoa 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.

History of uses

Antiprotozoal

Quinacrine was initially approved in the 1930s as an antimalarial drug. This antiprotozoal is also approved for the the treatment of Giardiasis (an intestinal parasite)^[3], 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 The product was one of the first synthetic substitutes for quinine although later superseded by chloroquine.

Anthelmintics

In addition it has been used for treating tapeworm infections.^[4]

Creutzfeldt-Jakob disease

Quinacrine has been shown to bind to the prion protein and prevent the formation of prion aggregates in vitro,^[5] 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,^[6] although other reports have shown no significant effect,^[7] and treatment of scrapie in mice and sheep has also shown no effect.^[8][9]

Quinacrine non-surgical sterilization for women (QS)

The use of quinacrine for non-surgical sterilization for women has also been researched. This method ^[10], was developed by Zipper et al. who reported a first year failure rate of 3.1%.^[11] 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 considerable controversy about the appropriateness of its use.^[1]

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.

Many peer reviewed studies suggest that,^[12] quinacrine sterilization (QS) is potentially safer than surgical sterilization.^[13][14]

References

External links

• The most extensive online database about quinacrine sterilization.
• Clinical Trial Results -- FDA Phase I clinical trial of quinacrine sterilization
• National Institute on Aging (NIA) trial
• Medical Research Council PRION-1 trial