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an antimalarial drug used to treat malaria and amebic dysentery and systemic lupus erythematosus

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/19 13:59:59」(JST)

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Chloroquine ( /ˈklɔrəkwɪn/) is a 4-aminoquinoline drug used in the treatment or prevention of malaria.

History

Chloroquine was discovered in 1934 by Hans Andersag and coworkers at the Bayer laboratories, who named it "Resochin".^[1] It was ignored for a decade because it was considered too toxic for human use. During World War II, United States government-sponsored clinical trials for antimalarial drug development showed unequivocally that chloroquine has a significant therapeutic value as an antimalarial drug. It was introduced into clinical practice in 1947 for the prophylactic treatment of malaria.^[2]

Uses

It has long been used in the treatment or prevention of malaria. After the malaria parasite Plasmodium falciparum started to develop widespread resistance to chloroquine,^[3]^[4] new potential uses of this cheap and widely available drug have been investigated. Chloroquine has been extensively used in mass drug administrations which may have contributed to the emergence and spread of resistance.

As it mildly suppresses the immune system, it is used in some autoimmune disorders, such as rheumatoid arthritis and lupus erythematosus.

Chloroquine is in clinical trials as an investigational antiretroviral in humans with HIV-1/AIDS and as a potential antiviral agent against chikungunya fever.^[5]

The radiosensitizing and chemosensitizing properties of chloroquine are beginning to be exploited in anticancer strategies in humans.^[6]^[7]

Pharmacokinetics

Chloroquine has a very high volume of distribution, as it diffuses into the body's adipose tissue. Chloroquine and related quinines have been associated with cases of retinal toxicity, particularly when provided at higher doses for longer times. Accumulation of the drug may result in deposits that can lead to blurred vision and blindness. With long-term doses, routine visits to an ophthalmologist are recommended.

Chloroquine is also a lysosomotropic agent, meaning it accumulates preferentially in the lysosomes of cells in the body. The pK_a for the quinoline nitrogen of chloroquine is 8.5, meaning it is about 10% deprotonated at physiological pH as calculated by the Henderson-Hasselbalch equation. This decreases to about 0.2% at a lysosomal pH of 4.6. Because the deprotonated form is more membrane-permeable than the protonated form, a quantitative "trapping" of the compound in lysosomes results. (A quantitative treatment of this phenomenon involves the pK_as of all nitrogens in the molecule; this treatment, however, suffices to show the principle.)

The lysosomotropic character of chloroquine is believed to account for much of its antimalarial activity; the drug concentrates in the acidic food vacuole of the parasite and interferes with essential processes. Its lysomotropic properties further allow for its use for in vitro experiments pertaining to intracellular lipid related diseases,^[8]^[9] autophagy, and apoptosis.^[10]

Malaria prevention

Resochin tablet package

Chloroquine can be used for preventing malaria from Plasmodium vivax, P. ovale and P. malariae. Popular drugs based on chloroquine phosphate (also called nivaquine) are Chloroquine FNA, Resochin and Dawaquin. Many areas of the world have widespread strains of chloroquine-resistant P. falciparum, so other antimalarials, such as mefloquine or atovaquone, may be advisable instead. Combining chloroquine with proguanil may be more effective against chloroquine-resistant P. falciparum than treatment with chloroquine alone, but is no longer recommended by the CDC due to the availability of more effective combinations.^[11] For children 14 years of age or below, the dose of chloroquine is 600 mg per week.^{[citation needed]}

Adverse effects

At the doses used for prevention of malaria, side effects include gastrointestinal problems, stomach ache, itch, headache, postural hypotension, nightmares and blurred vision.

Chloroquine-induced itching is very common among black Africans (70%), but much less common in other races. It increases with age, and is so severe as to stop compliance with drug therapy. It is increased during malaria fever; its severity is correlated to the malaria parasite load in blood. Some evidence indicates it has a genetic basis and is related to chloroquine action with opiate receptors centrally or peripherally.^[12]

When doses are extended over a number of months, a slow onset of mood changes (i.e., depression, anxiety) can occur. These may be more pronounced with higher doses used for treatment. Chloroquine tablets have an unpleasant metallic taste.

Another serious side effect is toxicity to the eye (specifically, central serous retinopathy). This only occurs with long-term use over many years. Patients on long-term chloroquine therapy should be screened at baseline and every five years.^[13] The daily safe maximum doses for eye toxicity can be computed from one's height and weight using this calculator.^[14]

Chloroquine is very dangerous in overdose. It is rapidly absorbed from the gut. In 1961, published studies showed three children who took overdoses died within 2.5 hours of taking the drug. While the amount of the overdose was not cited, the therapeutic index for chloroquine is known to be small.^[15]

According to research published in the journal PLoS ONE, an overuse of chloroquine treatment has led to the development of a specific strain of E. coli that is now resistant to the powerful antibiotic ciprofloxacin.^[16]

A metabolite of chloroquine - hydroxycloroquine - has a long half-life (32–56 days) in blood and a large volume of distribution (580-815 L/kg).^[17] The therapeutic, toxic and lethal ranges are usually considered to be 0.03 to 15 mg/l, 3.0 to 26 mg/l and 20 to 104 mg/l, respectively. However, nontoxic cases have been reported in the range 0.3 to 39 mg/l, suggesting individual tolerance to this agent may be more variable than previously recognised.^[17]

Mechanism of action

Antimalarial

Hemozoin formation in P. falciparum: many antimalarials are strong inhibitors of hemozoin crystal growth.

Inside red blood cells, the malarial parasite must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Digestion is carried out in a vacuole of the parasitic cell.

During this process, the parasite release the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a nontoxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals.

Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form the FP-chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion. In essence, the parasite cell drowns in its own metabolic products.^[18]

Resistance

Since the first documentation of P. falciparum chlorquine resistance in the 1950s, resistant strains have appeared throughout East and West Africa, Southeast Asia, and South America. The effectiveness of chloroquine against P. falciparum has declined as resistant strains of the parasite evolved. They effectively neutralize the drug via a mechanism that drains chloroquine away from the digestive vacuole. Chloroquine-resistant cells efflux chloroquine at 40 times the rate of chloroquine-sensitive cells; the related mutations trace back to transmembrane proteins of the digestive vacuole, including sets of critical mutations in the PfCRT gene (Plasmodium falciparum chloroquine resistance transporter). The mutated protein, but not the wild-type transporter, transports chloroquine when expressed in Xenopus oocytes and is thought to mediate chloroquine leak from its site of action in the digestive vacuole.^[19] Resistant parasites also frequently have mutated products of the ABC transporter PfMDR1 gene (Plasmodium falciparum multidrug resistance gene) although these mutations are thought to be of secondary importance compared to Pfcrt. Verapamil, a Ca²⁺ channel blocker, has been found to restore both the chloroquine concentration ability and sensitivity to this drug. Recently, an altered chloroquine-transporter protein CG2 of the parasite has been related to chloroquine resistance, but other mechanisms of resistance also appear to be involved.^[20]

Research on the mechanism of chloroquine and how the parasite has acquired chloroquine resistance is still ongoing, other mechanisms of resistance are likely.

Disease-modifying antirheumatic drugs

Against rheumatoid arthritis, it operates by inhibiting lymphocyte proliferation, phospholipase A2^{[disambiguation needed]}, antigen presentation in dendritic cells, release of enzymes from lysosomes, release of reactive oxygen species from macrophages, and production of IL-1.

Antiviral

As an antiviral agent, it impedes the completion of the viral life cycle by inhibiting some processes occurring within intracellular organelles and requiring a low pH. As for HIV-1, chloroquine inhibits the glycosylation of the viral envelope glycoprotein gp120, which occurs within the Golgi apparatus.

Other studies suggest quite the opposite, with chloroquine being a potent inhibitor of interferons and enhancer of viral replication.^[21]

Antitumor

The mechanisms behind the effects of chloroquine on cancer are currently being investigated. The best-known effects (investigated in clinical and preclinical studies) include radiosensitizing effects through lysosome permeabilization, and chemosensitizing effects through inhibition of drug efflux pumps (ATP-binding cassette transporters) or other mechanisms (reviewed in the second-to-last reference below).

References

^ Krafts K, Hempelmann E, Skórska-Stania A (2012). "From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy". Parasitol Res 11 (1): 1-6. doi:10.1007/s00436-012-2886-x. PMID 22411634.
^ "The History of Malaria, an Ancient Disease". Centers for Disease Control. http://www.cdc.gov/malaria/history/index.htm#chloroquine.
^ Plowe CV (2005). "Antimalarial drug resistance in Africa: strategies for monitoring and deterrence". Curr. Top. Microbiol. Immunol.. Current Topics in Microbiology and Immunology 295: 55–79. doi:10.1007/3-540-29088-5_3. ISBN 3-540-25363-7. PMID 16265887.
^ Uhlemann AC, Krishna S (2005). "Antimalarial multi-drug resistance in Asia: mechanisms and assessment". Curr. Top. Microbiol. Immunol.. Current Topics in Microbiology and Immunology 295: 39–53. doi:10.1007/3-540-29088-5_2. ISBN 3-540-25363-7. PMID 16265886.
^ Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R (November 2003). "Effects of chloroquine on viral infections: an old drug against today's diseases?". Lancet Infect Dis 3 (11): 722–7. doi:10.1016/S1473-3099(03)00806-5. PMID 14592603. http://linkinghub.elsevier.com/retrieve/pii/S1473309903008065.
^ Savarino A, Lucia MB, Giordano F, Cauda R (October 2006). "Risks and benefits of chloroquine use in anticancer strategies". Lancet Oncol. 7 (10): 792–3. doi:10.1016/S1470-2045(06)70875-0. PMID 17012039. http://linkinghub.elsevier.com/retrieve/pii/S1470-2045(06)70875-0.
^ Sotelo J, Briceño E, López-González MA (March 2006). "Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial". Ann. Intern. Med. 144 (5): 337–43. PMID 16520474.
"Summaries for patients. Adding chloroquine to conventional chemotherapy and radiotherapy for glioblastoma multiforme". Ann. Intern. Med. 144 (5): I31. March 2006. PMID 16520470.
^ Chen, Patrick; Gombart, Z and Chen J (2011). "Chloroquine treatment of ARPE-19 cells leads to lysosome dilation and intracellular lipid accumulation: possible implications of lysosomal dysfunction in macular degeneration". Cell & Bioscience 1 (10): 10. doi:10.1186/2045-3701-1-10. http://www.cellandbioscience.com/content/1/1/10.
^ Kurup, Pradeep; Zhang Y, Xu J, et al. (2010). "Aβ–mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61". Neurobiology of Disease 30 (17): 5948–57. doi:10.1523/JNEUROSCI.0157-10.2010. PMC 2868326. PMID 20427654. http://www.jneurosci.org/content/30/17/5948.short.
^ Kim, Ella; Wustenberg R, Rusbam A, et al (2010). "Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells". Neuro-oncology 12 (4): 389–400. doi:10.1093/neuonc/nop046. PMC 2940600. PMID 20308316. http://neuro-oncology.oxfordjournals.org/content/12/4/389.short.
^ CDC. Health information for international travel 2001-2002. Atlanta, Georgia: U.S. Department of Health and Human Services, Public Health Service, 2001.
^ Ajayi AA (September 2000). "Mechanisms of chloroquine-induced pruritus". Clin. Pharmacol. Ther. 68 (3): 336. PMID 11014416.
^ Michaelides M, Stover NB, Francis PJ, Weleber RG (2011). "Retinal toxicity associated with hydroxychloroquine and chloroquine: risk factors, screening, and progression despite cessation of therapy". Arch Ophthalmol 129 (1): 30–9. PMID 21220626.
^ "numericalexample.com - Determine the safe dose of medicines: Chloroquine and Hydroxychloroquine (Plaquenil)". http://www.numericalexample.com/content/view/24/33. Retrieved 21 February 2008.
^ Cann HM, Verhulst HL (1 January 1961). "Fatal acute chloroquine poisoning in children" (abstract). Pediatrics 27 (1): 95–102. PMID 13690445. http://pediatrics.aappublications.org/cgi/content/abstract/27/1/95?ijkey=0c507c09d8450f8c8bbadf109d6428e93ad2619f&keytype2=tf_ipsecsha.
^ Davidson RJ, Davis I, Willey BM (2008). Frenck, Robert. ed. "Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America". PLoS ONE 3 (7): e2727. Bibcode 2008PLoSO...3.2727D. doi:10.1371/journal.pone.0002727. PMC 2481278. PMID 18648533. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2481278/.
^ ^a ^b Molina DK (2011) Postmortem hydroxychloroquine concentrations in nontoxic cases. Am J Forensic Med Pathol
^ Hempelmann E. (2007). "Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors". Parasitol Research 100 (4): 671–676. doi:10.1007/s00436-006-0313-x. PMID 17111179.
^ Martin RE, Marchetti RV, Cowan AI et al.(September 2009). "Chloroquine transport via the malaria parasite's chloroquine resistance transporter". Science 325(5948): 1680-2:
^ Essentials of medical pharmacology fifth edition 2003,reprint 2004, published by-Jaypee Brothers Medical Publisher Ltd, 2003,KD tripathi, page 739,740.
^ "Malaria and HIV/AIDS". MalariaSite.com. http://www.malariasite.com/malaria/malariainaids.htm.

External links

Chloroquine Anti-HIV action
Chloroquine and imatinib

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 旅行者におけるマラリア感染の予防 prevention of malaria infection in travelers
2. 熱帯熱マラリア以外のマラリアの概要 overview of non falciparum malaria
3. 抗マラリア剤：概要 antimalarial drugs an overview
4. Diseases potentially acquired by travel to South Asia
5. 合併症のない熱帯熱マラリアの治療 treatment of uncomplicated falciparum malaria

English Journal

Validation of a method for the simultaneous quantification of chloroquine, desethylchloroquine and primaquine in plasma by HPLC-DAD.

Zuluaga-Idárraga L1, Yepes-Jiménez N1, López-Córdoba C2, Blair-Trujillo S1.Author information 1Grupo Malaria, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.2Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Medellín, Colombia. Electronic address: carlopezudea@gmail.com.AbstractOne of the most important aspects regarding the therapeutic efficacy of antimalarials is its quantification in biologic fluids. The detection and measurement of antimalarial drug levels is important for demonstrating (1) adequate absorption of the drug being given, (2) compliance in taking the full regimen required for treatment and (3) the level of drug in the blood at any time during the test period that parasites reappear. There is a lack of validated methods that simultaneously quantify different antimalarials administered at the same time, such as the use of chloroquine (CQ) and primaquine (PQ) in infections caused by Plasmodium vivax. In this study, a bioanalytical method was validated for the simultaneous quantification of primaquine (PQ), chloroquine (CQ) and desethylchloroquine (DSCQ) in human plasma using liquid-liquid extraction and high performance liquid chromatography with a diode array detector (HPLC-DAD). The PQ was evaluated over a concentration range of 100-3000nM and the CQ and DSCQ was evaluated over a concentration range of 20-2000nM. The selectivity of the method was verified by checking for interference by commonly used antimalarials and plasma samples. The accuracy and precision of the method was assessed for drugs spiked into human plasma and recoveries of 83.7%, 92.3%, and 76.5% were obtained for CQ, DSCQ, and PQ, respectively. The applicability of this method was also demonstrated with blood samples from patients with vivax malaria that received combination CQ plus PQ treatment. The simultaneous detection and accurate measurement of CQ, DSCQ, and PQ levels in human plasma provides an important and economical method for validating and monitoring sensitivity/resistance of P. vivax to more common treatment regimen.
Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2014 Jul;95:200-6. doi: 10.1016/j.jpba.2014.03.006. Epub 2014 Mar 12.
One of the most important aspects regarding the therapeutic efficacy of antimalarials is its quantification in biologic fluids. The detection and measurement of antimalarial drug levels is important for demonstrating (1) adequate absorption of the drug being given, (2) compliance in taking the full
PMID 24682018

Synthesis and in vitro biological evaluation of aminoacridines and artemisinin-acridine hybrids.

Joubert JP1, Smit FJ1, du Plessis L2, Smith PJ3, N'da DD4.Author information 1Department of Pharmaceutical Chemistry, North-West University, Potchefstroom 2520, South Africa.2Centre of Excellence for Pharmaceutical Sciences (PHARMCEN), North-West University, Potchefstroom 2520, South Africa.3Department of Pharmacology, University of Cape Town, Groote Schuur Hospital, Observatory 7925, South Africa.4Centre of Excellence for Pharmaceutical Sciences (PHARMCEN), North-West University, Potchefstroom 2520, South Africa. Electronic address: david.nda@nwu.ac.za.AbstractDuring this study, 9-aminoacridine and artemisinin-acridine hybrid compounds were synthesized and the in vitro for antimalarial activity against both the chloroquine sensitive but also gametocytocidal strain (NF54), and chloroquine resistant (Dd2) strains of Plasmodium falciparum was determined. In vitro cytotoxicity against CHO cells, apoptosis of HepG2 and SH-SY5Y as well as anticancer activity against HeLa cell lines were assessed. The hybrids were synthesized, using a microwave-assisted radiation method by covalently linking artemisinin and acridine pharmacophores by means of a liable, aminoethyl ether linker. The synthesized compounds were found active against both the Plasmodium strains and displayed superior selective toxicity towards the parasitic cells. Hybrid 7, however, containing ethylenediamine linker, proved the most active of all of the synthesized compounds. It had seven-fold higher antigametocytocidal activity compared to chloroquine and was also found to be seven-fold more potent than chloroquine against the Dd2 strain, with highly selective action towards the parasitic cells. This hybrid also showed favourable anti-cancer activity against the HeLa cells, three- and eight-fold higher than those of chloroquine and melphalan, respectively. This hybrid may therefore stand as drug candidate for further investigation in the search for new and effective drugs against malaria and cervical cancer.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 Jun 2;56:16-27. doi: 10.1016/j.ejps.2014.01.014. Epub 2014 Feb 18.
During this study, 9-aminoacridine and artemisinin-acridine hybrid compounds were synthesized and the in vitro for antimalarial activity against both the chloroquine sensitive but also gametocytocidal strain (NF54), and chloroquine resistant (Dd2) strains of Plasmodium falciparum was determined. In
PMID 24560941

Autophagy contributes to dasatinib-induced myeloid differentiation of human acute myeloid leukemia cells.

Xie N1, Zhong L1, Liu L1, Fang Y1, Qi X1, Cao J1, Yang B1, He Q1, Ying M2.Author information 1Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.2Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: mying@zju.edu.cn.AbstractA breakthrough in clinical oncology was achieved as All-trans-retinoic acid (ATRA) sparked intensive differentiation therapy research. However, differentiation therapy is limited because ATRA is the sole efficient agent. Dasatinib is reported to induce myeloid differentiation of acute myeloid leukemia (AML) cells in vitro, but its mechanism remains unclear. Furthermore, the ability of dasatinib to cause differentiation of AML cells has not yet been proven. We assessed the contribution of autophagy to dasatinib-induced differentiation of AML cells. We found that dasatinib induces myeloid differentiation of AML cells accompanied with autophagy induction. Pharmacological inhibition of autophagy by 3-MA, Wortmannin, LY294002 and chloroquine block dasatinib-induced AML cell differentiation, whereas the induction of autophagy by rapamycin enhances AML cell differentiation. Our results suggest that retinoic acid receptors alpha (RARα) may not be involved in dasatinib-induced differentiation. In addition, we further illustrated that even low concentration of dasatinib can enhance ATRA-induced differentiation capability through initiation of autophagy. Taken together, we conclude that autophagy enhances the dasatinib-induced differentiation, which may provide theoretical support for developing dasatinib as a promising strategy for future differentiation therapy in AML patients.
Biochemical pharmacology.Biochem Pharmacol.2014 May 1;89(1):74-85. doi: 10.1016/j.bcp.2014.02.019. Epub 2014 Mar 4.
A breakthrough in clinical oncology was achieved as All-trans-retinoic acid (ATRA) sparked intensive differentiation therapy research. However, differentiation therapy is limited because ATRA is the sole efficient agent. Dasatinib is reported to induce myeloid differentiation of acute myeloid leukem
PMID 24607273

Japanese Journal

インスリン様成長因子-1(IGF-1)は実験的クロロキン誘発縁取り空胞ミオパチーの筋線維における空胞の過剰形成を抑制する

熊本俊秀,中村憲一郎,仲野義和,河村由子,麻生泰弘,迫祐介,木村成志
九州看護福祉大学紀要 = The journal of Kyushu University of Nursing and Social Welfare 15(1), 3-11, 2015-03
… Objective: We investigated the effect of insulin-like growth factor-1 (IGF-1) on the histological (e.g., rimmed vacuoles and muscle fiber atrophy) and molecular properties of the denervated muscles of chloroquine-treated rats. … Methods: The left hind-legs of adult male Wistar rats were denervated by ligation of the sciatic nerve.The rats with and without chloroquine treatment were given saline or IGF-1 intraperitoneally at a daily dose of either 2 or 8 mg/kg for 8 days. …
NAID 120005612335

インスリン様成長因子-1(IGF-1)は実験的クロロキン誘発縁取り空胞ミオパチーの筋線維における空胞の過剰形成を抑制する

熊本俊秀,中村憲一郎,仲野義和 [他],河村由子,麻生泰弘,迫祐介,木村成志
九州看護福祉大学紀要 15(1), 3-11, 2015-03
NAID 110009889137

Niemann-Pick disease type C2 protein induces autophagy and inhibits growth in FM3A breast cancer cells

, , ,
Drug Discoveries & Therapeutics advpub(0), 2015
… When silkworm NPC2 was used to inhibit FM3A cell growth, that inhibition was attenuated by chloroquine, which inhibits autophagic activity by preventing lysosomal acidification. …
NAID 130005064607

Related Pictures

★リンクテーブル★

リンク元	「クロロキン」
拡張検索	「hydroxychloroquine」

「クロロキン」

Chloroquine
Systematic (IUPAC) name
	(RS)-N'-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine
Clinical data
Trade names	Aralen
AHFS/Drugs.com	monograph
Licence data	US FDA:link
Pregnancy cat.	?
Legal status	℞-only (US)
Pharmacokinetic data
Metabolism	Liver
Half-life	1-2 months
Identifiers
CAS number	54-05-7
ATC code	P01BA01
PubChem	CID 2719
DrugBank	DB00608
ChemSpider	2618
UNII	886U3H6UFF
KEGG	D02366
ChEBI	CHEBI:3638
ChEMBL	CHEMBL76
NIAID ChemDB	000733
Chemical data
Formula	C18H26ClN3
Mol. mass	319.872 g/mol
	SMILES Clc1cc2nccc(c2cc1)NC(C)CCCN(CC)CC;
	InChI InChI=1S/C18H26ClN3/c1-4-22(5-2)12-6-7-14(3)21-17-10-11-20-18-13-15(19)8-9-16(17)18/h8-11,13-14H,4-7,12H2,1-3H3,(H,20,21) ; Key:WHTVZRBIWZFKQO-UHFFFAOYSA-N ;
(what is this?) (verify);

　　[★]

英: chloroquine
ラ: chloroquini
関

マラリア原虫による感染症の治療薬
副作用：クロロキン網膜症
治療薬、のほか予防薬としても使用される。
耐性の原虫が出現してきている。

「hydroxychloroquine」

　　[★] ヒドロキシクロロキン

同: Plaquenil

[1] Krafts K, Hempelmann E, Skórska-Stania A (2012). "From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy". Parasitol Res 11 (1): 1-6. doi:10.1007/s00436-012-2886-x. PMID 22411634.

[2] "The History of Malaria, an Ancient Disease". Centers for Disease Control. http://www.cdc.gov/malaria/history/index.htm#chloroquine.

[3] Plowe CV (2005). "Antimalarial drug resistance in Africa: strategies for monitoring and deterrence". Curr. Top. Microbiol. Immunol.. Current Topics in Microbiology and Immunology 295: 55–79. doi:10.1007/3-540-29088-5_3. ISBN 3-540-25363-7. PMID 16265887.

[4] Uhlemann AC, Krishna S (2005). "Antimalarial multi-drug resistance in Asia: mechanisms and assessment". Curr. Top. Microbiol. Immunol.. Current Topics in Microbiology and Immunology 295: 39–53. doi:10.1007/3-540-29088-5_2. ISBN 3-540-25363-7. PMID 16265886.

[5] Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R (November 2003). "Effects of chloroquine on viral infections: an old drug against today's diseases?". Lancet Infect Dis 3 (11): 722–7. doi:10.1016/S1473-3099(03)00806-5. PMID 14592603. http://linkinghub.elsevier.com/retrieve/pii/S1473309903008065.

[6] Savarino A, Lucia MB, Giordano F, Cauda R (October 2006). "Risks and benefits of chloroquine use in anticancer strategies". Lancet Oncol. 7 (10): 792–3. doi:10.1016/S1470-2045(06)70875-0. PMID 17012039. http://linkinghub.elsevier.com/retrieve/pii/S1470-2045(06)70875-0.

[7] Sotelo J, Briceño E, López-González MA (March 2006). "Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial". Ann. Intern. Med. 144 (5): 337–43. PMID 16520474.
"Summaries for patients. Adding chloroquine to conventional chemotherapy and radiotherapy for glioblastoma multiforme". Ann. Intern. Med. 144 (5): I31. March 2006. PMID 16520470.

[8] Chen, Patrick; Gombart, Z and Chen J (2011). "Chloroquine treatment of ARPE-19 cells leads to lysosome dilation and intracellular lipid accumulation: possible implications of lysosomal dysfunction in macular degeneration". Cell & Bioscience 1 (10): 10. doi:10.1186/2045-3701-1-10. http://www.cellandbioscience.com/content/1/1/10.

[9] Kurup, Pradeep; Zhang Y, Xu J, et al. (2010). "Aβ–mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61". Neurobiology of Disease 30 (17): 5948–57. doi:10.1523/JNEUROSCI.0157-10.2010. PMC 2868326. PMID 20427654. http://www.jneurosci.org/content/30/17/5948.short.

[10] Kim, Ella; Wustenberg R, Rusbam A, et al (2010). "Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells". Neuro-oncology 12 (4): 389–400. doi:10.1093/neuonc/nop046. PMC 2940600. PMID 20308316. http://neuro-oncology.oxfordjournals.org/content/12/4/389.short.

[11] CDC. Health information for international travel 2001-2002. Atlanta, Georgia: U.S. Department of Health and Human Services, Public Health Service, 2001.

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