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Hemoglobin is composed of a protein unit (digested by the parasite) and a heme unit (not used by the parasite). During this process, the parasite releases 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.{{citation needed|date=July 2015}}
Hemoglobin is composed of a protein unit (digested by the parasite) and a heme unit (not used by the parasite). During this process, the parasite releases 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.{{citation needed|date=July 2015}}


Chloroquine enters the red blood cell, inhibiting the 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.<ref>{{cite journal | vauthors = Hempelmann E | title = Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors | journal = Parasitology Research | volume = 100 | issue = 4 | pages = 671–6 | date = March 2007 | pmid = 17111179 | doi = 10.1007/s00436-006-0313-x }}</ref> Parasites that do not form hemozoin are therefore resistant to chloroquine.<ref name="Lin2015">{{cite journal | vauthors = Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, Ravelli RB, Aime E, Capuccini B, Mommaas-Kienhuis AM, O'Toole T, Prins F, Franke-Fayard BM, Ramesar J, Chevalley-Maurel S, Kroeze H, Koster AJ, Tanke HJ, Crisanti A, Langhorne J, Arese P, Van den Steen PE, Janse CJ, Khan SM | display-authors = 6 | title = Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance | journal = The Journal of Experimental Medicine | volume = 212 | issue = 6 | pages = 893–903 | date = June 2015 | pmid = 25941254 | pmc = 4451122 | doi = 10.1084/jem.20141731 | url = https://lirias.kuleuven.be/bitstream/123456789/500975/3/2015113.pdf }}</ref>
Chloroquine enters the red blood cell by simple diffusion, inhibiting the parasite cell and digestive vacuole. 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.<ref>{{cite journal | vauthors = Hempelmann E | title = Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors | journal = Parasitology Research | volume = 100 | issue = 4 | pages = 671–6 | date = March 2007 | pmid = 17111179 | doi = 10.1007/s00436-006-0313-x }}</ref> Parasites that do not form hemozoin are therefore resistant to chloroquine.<ref name="Lin2015">{{cite journal | vauthors = Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, Ravelli RB, Aime E, Capuccini B, Mommaas-Kienhuis AM, O'Toole T, Prins F, Franke-Fayard BM, Ramesar J, Chevalley-Maurel S, Kroeze H, Koster AJ, Tanke HJ, Crisanti A, Langhorne J, Arese P, Van den Steen PE, Janse CJ, Khan SM | display-authors = 6 | title = Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance | journal = The Journal of Experimental Medicine | volume = 212 | issue = 6 | pages = 893–903 | date = June 2015 | pmid = 25941254 | pmc = 4451122 | doi = 10.1084/jem.20141731 | url = https://lirias.kuleuven.be/bitstream/123456789/500975/3/2015113.pdf }}</ref>


==== Resistance in malaria ====
==== Resistance in malaria ====

Revision as of 07:00, 18 March 2020

Chloroquine
Clinical data
Pronunciation/ˈklɔːrəkwɪn/
Trade namesAralen, others
AHFS/Drugs.comMonograph
License data
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver
Elimination half-life1–2 months
Identifiers
  • (RS)-N'-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.000.175 Edit this at Wikidata
Chemical and physical data
FormulaC18H26ClN3
Molar mass319.872 g/mol g·mol−1
3D model (JSmol)
  • Clc1cc2nccc(c2cc1)NC(C)CCCN(CC)CC
  • 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) checkY
  • Key:WHTVZRBIWZFKQO-UHFFFAOYSA-N checkY
  (verify)

Chloroquine is a medication used to prevent and to treat malaria in areas where malaria is known to be sensitive to its effects.[1] Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication.[1] It is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus.[1] It is taken by mouth.[1]

Common side effects include muscle problems, loss of appetite, diarrhea, and skin rash.[1] Serious side effects include problems with vision, muscle damage, seizures, and low blood cell levels.[1] It appears to be safe for use during pregnancy.[1][2] Chloroquine is a member of the drug class 4-aminoquinoline.[1] It works against the asexual form of malaria inside the red blood cell.[1]

Chloroquine was discovered in 1934 by Hans Andersag.[3][4] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[5] It is available as a generic medication.[1] The wholesale cost in the developing world is about US$0.04.[6] In the United States, it costs about US$5.30 per dose.[1]

Medical uses

Resochin tablet package

Malaria

Chloroquine has long been used in the treatment or prevention of malaria from Plasmodium vivax, P. ovale, and P. malariae, excluding the malaria parasite Plasmodium falciparum, for it started to develop widespread resistance to it.[7][8]

Chloroquine has been extensively used in mass drug administrations, which may have contributed to the emergence and spread of resistance. It is recommended to check if chloroquine is still effective in the region prior to using it.[9] In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead. The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations.[10]

Amebiasis

In treatment of amoebic liver abscess, chloroquine may be used instead of or in addition to other medications in the event of failure of improvement with metronidazole or another nitroimidazole within 5 days or intolerance to metronidazole or a nitroimidazole.[11]

Rheumatic disease

As it mildly suppresses the immune system, it is used in some autoimmune disorders, such as rheumatoid arthritis and lupus erythematosus.[1]

Coronavirus

In trials conducted in China, chloroquine appears to be useful for coronavirus disease 2019.[12] See § Research for details.

Adverse effects

Side effects include neuromuscular, hearing, gastrointestinal, brain, skin, eye, cardiovascular (rare), and blood reactions.[13]

  • Seizures[13]
  • Deafness or tinnitus.[13]
  • Nausea, vomiting, diarrhea, abdominal cramps, and anorexia.[13]
  • Mild and transient headache.[13]
  • Skin itchiness, skin color changes, hair loss, and skin rashes.[13]
    • 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.[14]
  • Unpleasant metallic taste
    • This could be avoided by "taste-masked and controlled release" formulations such as multiple emulsions.[15]
  • Chloroquine retinopathy
    • May be irreversible.[13] This occurs with long-term use over many years or with high doses. Patients on long-term chloroquine therapy should be screened at baseline and then annually after five years of use.[16] Patients should be screened for vision changes such as blurring of vision, difficulty focusing, or seeing half an object.[13]
  • Hypotension and electrocardiographic changes[13][17]
    • This manifests itself as either conduction disturbances (bundle-branch block, atrioventricular block) or cardiomyopathy – often with hypertrophy, restrictive physiology, and congestive heart failure. The changes may be irreversible. Only two cases have been reported requiring heart transplantation, suggesting this particular risk is very low. Electron microscopy of cardiac biopsies show pathognomonic cytoplasmic inclusion bodies.
  • Pancytopenia, aplastic anemia, reversible agranulocytosis, low blood platlets, neutropenia.[18]

Pregnancy

Chloroquine has not been shown to have any harmful effects on the fetus when used for malarial prophylaxis.[19] Small amounts of chloroquine are excreted in the breast milk of lactating women. However, because this drug can be safely prescribed to infants, the effects are not harmful. Studies with mice show that radioactively tagged chloroquine passed through the placenta rapidly and accumulated in the fetal eyes which remained present five months after the drug was cleared from the rest of the body.[18][20] It is still advised to prevent women who are pregnant or planning on getting pregnant from traveling to malaria-risk regions.[19]

Elderly

There is not enough evidence to determine whether chloroquine is safe to be given to people aged 65 and older. However, the drug is cleared by the kidneys and toxicity should be monitored carefully in people with poor kidney functions.[18]

Drug interactions

  • Ampicillin- levels may be reduced by chloroquine
  • Antacids- may reduce absorption of chloroquine
  • Cimetidine- may inhibit metabolism of chloroquine; increasing levels of chloroquine in the body
  • Cyclosporine- levels may be increased by chloroquine
  • Kaolin- may reduce absorption of chloroquine
  • Mefloquine- may increase risk of convulsions[18]

Overdose

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.[21] Symptoms of overdose include headache, drowsiness, visual disturbances, nausea and vomiting, cardiovascular collapse, seizures, and sudden respiratory and cardiac arrest.[18]

An analog of chloroquine – hydroxychloroquine – has a long half-life (32–56 days) in blood and a large volume of distribution (580–815 L/kg).[22] 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 up to 39 mg/l, suggesting individual tolerance to this agent may be more variable than previously recognised.[22]

Pharmacology

  • Absorption: Rapid and almost completely
  • Distribution: Widely distributed into body tissues
  • Protein binding: 55%
  • Metabolism: Partially hepatic to main metabolite, desethylchloroquine
  • Excretion: Urine (≥50% as unchanged drug); acidification of urine increases elimination

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.[citation needed]

Chloroquine is also a lysosomotropic agent, meaning it accumulates preferentially in the lysosomes of cells in the body. The pKa 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 pKas of all nitrogens in the molecule; this treatment, however, suffices to show the principle.)[citation needed]

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 lysosomotropic properties further allow for its use for in vitro experiments pertaining to intracellular lipid related diseases,[23][24] autophagy, and apoptosis.[25]

Mechanism of action

Malaria

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

Inside red blood cells, the malarial parasite, which is then in its asexual lifecycle stage, 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.[citation needed]

Hemoglobin is composed of a protein unit (digested by the parasite) and a heme unit (not used by the parasite). During this process, the parasite releases 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.[citation needed]

Chloroquine enters the red blood cell by simple diffusion, inhibiting the parasite cell and digestive vacuole. 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.[26] Parasites that do not form hemozoin are therefore resistant to chloroquine.[27]

Resistance in malaria

Since the first documentation of P. falciparum chloroquine 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 P. falciparum chloroquine resistance transporter (PfCRT) gene. 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.[28] Resistant parasites also frequently have mutated products of the ABC transporter P. falciparum multidrug resistance (PfMDR1) 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.[29] Research on the mechanism of chloroquine and how the parasite has acquired chloroquine resistance is still ongoing, as other mechanisms of resistance are likely.[citation needed]

Other agents which have been shown to reverse chloroquine resistance in malaria are chlorpheniramine, gefitinib, imatinib, tariquidar and zosuquidar.[30]

Antiviral

Chloroquine has antiviral effects,[31] which works by increasing endosomal pH required for the virus/cell fusion process[32][33]

Other

Chloroquine inhibits thiamine uptake.[34] It acts specifically on the transporter SLC19A3.

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

History

Its history goes back to Peru (South America), where the indigenous people extracted the bark of the Cinchona[35] trees and used the extract (Chinchona officinalis) to fight chills and fever in the seventeenth century. In 1633 this herbal medicine was introduced in Europe, where it was given the same use and also began to be used against malaria.[36] The quinoline antimalarial drug quinine was isolated from the extract in 1820, and chloroquine is an analogue of this.

Chloroquine was discovered in 1934 by Hans Andersag and coworkers at the Bayer laboratories, who named it "Resochin".[37] 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.[38]

Names

Brand names include Chloroquine FNA, Resochin, Dawaquin, and Lariago.[39]

Research

SARS-CoV-2

For coronaviruses chloroquine works by increasing endosomal pH and interfere with terminal glycosylation of the cellular receptor.[40][41] In late January 2020 during the 2019–20 coronavirus outbreak, Chinese medical researchers stated that exploratory research into chloroquine and two other medications, remdesivir and lopinavir/ritonavir, seemed to have "fairly good inhibitory effects" on the 2019 novel coronavirus. Requests to start clinical testing were submitted.[42][43][44] Chloroquine phosphate had been also proposed as a treatment for SARS-CoV with in vitro tests successfully inhibiting the virus.[45]

On 19 February 2020, preliminary results found that chloroquine may be effective and safe in treating COVID-19 associated pneumonia.[12][46] There is evidence to indicate the efficacy of chloroquine phosphate against SARS-CoV-2 in vitro, on Vero cells.[47] The Guangdong Provincial Department of Science and Technology and the Guangdong Provincial Health and Health Commission issued a report stating that chloroquine phosphate "improves the success rate of treatment and shortens the length of patient’s hospital stay" and recommended it for patients diagnosed with mild, moderate and severe cases of novel coronavirus pneumonia.[48]

Other viruses

Chloroquine is being considered in pre-clinical models as a potential agent against chikungunya fever.[49]

Other

The radiosensitizing and chemosensitizing properties of chloroquine are beginning to be exploited in anticancer strategies in humans.[50][51] In biomedicinal science, chloroquine is used for in vitro experiments to inhibit lysosomal degradation of protein products.

References

  1. ^ a b c d e f g h i j k l "Aralen Phosphate". The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 2 December 2015.
  2. ^ "Chloroquine Use During Pregnancy". Drugs.com. Retrieved 16 April 2019. There are no controlled data in human pregnancies.
  3. ^ Manson P, Cooke G, Zumla A, eds. (2009). Manson's tropical diseases (22nd ed.). [Edinburgh]: Saunders. p. 1240. ISBN 9781416044703.
  4. ^ Bhattacharjee, Mrinal (2016). Chemistry of Antibiotics and Related Drugs. Springer. p. 184. ISBN 9783319407463. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  5. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. ^ "Chloroquine (Base)". International Drug Price Indicator Guide. Retrieved 4 December 2015.
  7. ^ Plowe CV (2005). "Antimalarial drug resistance in Africa: strategies for monitoring and deterrence". Malaria: Drugs, Disease and Post-genomic Biology. Current Topics in Microbiology and Immunology. Vol. 295. pp. 55–79. doi:10.1007/3-540-29088-5_3. ISBN 3-540-25363-7. PMID 16265887.
  8. ^ Uhlemann AC, Krishna S (2005). "Antimalarial multi-drug resistance in Asia: mechanisms and assessment". Malaria: Drugs, Disease and Post-genomic Biology. Current Topics in Microbiology and Immunology. Vol. 295. pp. 39–53. doi:10.1007/3-540-29088-5_2. ISBN 3-540-25363-7. PMID 16265886.
  9. ^ "DailyMed – CHLOROQUINE- chloroquine phosphate tablet CHLOROQUINE- chloroquine phosphate tablet, coated". dailymed.nlm.nih.gov. Archived from the original on 8 December 2015. Retrieved 4 November 2015.
  10. ^ CDC. Health information for international travel 2001–2002. Atlanta, Georgia: U.S. Department of Health and Human Services, Public Health Service, 2001.
  11. ^ Amebic Hepatic Abscesses~treatment at eMedicine
  12. ^ a b Gao J, Tian Z, Yang X (February 2020). "Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies". Bioscience Trends. 14: 72–73. doi:10.5582/bst.2020.01047. PMID 32074550.
  13. ^ a b c d e f g h i "DailyMed – CHLOROQUINE- chloroquine phosphate tablet CHLOROQUINE- chloroquine phosphate tablet, coated". dailymed.nlm.nih.gov. Archived from the original on 8 December 2015. Retrieved 3 November 2015.
  14. ^ Ajayi AA (September 2000). "Mechanisms of chloroquine-induced pruritus". Clinical Pharmacology and Therapeutics. 68 (3): 336. PMID 11014416.
  15. ^ Vaziri A, Warburton B (1994). "Slow release of chloroquine phosphate from multiple taste-masked W/O/W multiple emulsions". Journal of Microencapsulation. 11 (6): 641–8. doi:10.3109/02652049409051114. PMID 7884629.
  16. ^ Michaelides M, Stover NB, Francis PJ, Weleber RG (January 2011). "Retinal toxicity associated with hydroxychloroquine and chloroquine: risk factors, screening, and progression despite cessation of therapy". Archives of Ophthalmology. 129 (1): 30–9. doi:10.1001/archophthalmol.2010.321. PMID 21220626.
  17. ^ Tönnesmann E, Kandolf R, Lewalter T (June 2013). "Chloroquine cardiomyopathy – a review of the literature". Immunopharmacology and Immunotoxicology. 35 (3): 434–42. doi:10.3109/08923973.2013.780078. PMID 23635029.
  18. ^ a b c d e "Aralen Chloroquine Phosphate, USP" (PDF). Archived (PDF) from the original on 8 December 2015. Retrieved 5 November 2015.
  19. ^ a b "Malaria – Chapter 3 – 2016 Yellow Book". wwwnc.cdc.gov. Archived from the original on 14 January 2016. Retrieved 11 November 2015.
  20. ^ Ullberg S, Lindquist NG, Sjòstrand SE (September 1970). "Accumulation of chorio-retinotoxic drugs in the foetal eye". Nature. 227 (5264): 1257–8. Bibcode:1970Natur.227.1257U. doi:10.1038/2271257a0. PMID 5452818.
  21. ^ Cann HM, Verhulst HL (January 1961). "Fatal acute chloroquine poisoning in children". Pediatrics. 27: 95–102. PMID 13690445.
  22. ^ a b Molina DK (March 2012). "Postmortem hydroxychloroquine concentrations in nontoxic cases". The American Journal of Forensic Medicine and Pathology. 33 (1): 41–2. doi:10.1097/PAF.0b013e3182186f99. PMID 21464694.
  23. ^ Chen PM, Gombart ZJ, Chen JW (March 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 (1): 10. doi:10.1186/2045-3701-1-10. PMC 3125200. PMID 21711726.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  24. ^ Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, et al. (April 2010). "Abeta-mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61". The Journal of Neuroscience. 30 (17): 5948–57. doi:10.1523/JNEUROSCI.0157-10.2010. PMC 2868326. PMID 20427654.
  25. ^ Kim EL, Wüstenberg R, Rübsam A, Schmitz-Salue C, Warnecke G, Bücker EM, et al. (April 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.
  26. ^ Hempelmann E (March 2007). "Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors". Parasitology Research. 100 (4): 671–6. doi:10.1007/s00436-006-0313-x. PMID 17111179.
  27. ^ Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, et al. (June 2015). "Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance" (PDF). The Journal of Experimental Medicine. 212 (6): 893–903. doi:10.1084/jem.20141731. PMC 4451122. PMID 25941254.
  28. ^ Martin RE, Marchetti RV, Cowan AI, Howitt SM, Bröer S, Kirk K (September 2009). "Chloroquine transport via the malaria parasite's chloroquine resistance transporter". Science. 325 (5948): 1680–2. Bibcode:2009Sci...325.1680M. doi:10.1126/science.1175667. PMID 19779197.
  29. ^ Essentials of medical pharmacology fifth edition 2003, reprint 2004, published by-Jaypee Brothers Medical Publisher Ltd, 2003, KD Tripathi, pages 739,740.
  30. ^ Alcantara LM, Kim J, Moraes CB, Franco CH, Franzoi KD, Lee S, et al. (June 2013). "Chemosensitization potential of P-glycoprotein inhibitors in malaria parasites". Experimental Parasitology. 134 (2): 235–43. doi:10.1016/j.exppara.2013.03.022. PMID 23541983.
  31. ^ 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?". The Lancet. Infectious Diseases. 3 (11): 722–7. doi:10.1016/s1473-3099(03)00806-5. PMID 14592603.
  32. ^ Al‐Bari, Md. Abdul Alim (18 March 2020). "Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases". Pharmacology Research & Perspectives. 5 (1). doi:10.1002/prp2.293. PMID 28596841. Retrieved 18 March 2020.
  33. ^ Fredericksen, Brenda L.; Wei, Bangdong L.; Yao, Jian; Luo, Tianci; Garcia, J. Victor. "Inhibition of Endosomal/Lysosomal Degradation Increases the Infectivity of Human Immunodeficiency Virus". Journal of Virology. 76 (22). doi:10.1128/JVI.76.22.11440-11446.2002. PMID 12388705. Retrieved 18 March 2020.
  34. ^ Huang Z, Srinivasan S, Zhang J, Chen K, Li Y, Li W, et al. (2012). "Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy". PLOS Genetics. 8 (11): e1003083. doi:10.1371/journal.pgen.1003083. PMC 3510038. PMID 23209439.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  35. ^ Fern, Ken (2010–2020). "Cinchona officinalis – L." Plans for a Future. Retrieved 2 February 2020.{{cite web}}: CS1 maint: date format (link) CS1 maint: url-status (link)
  36. ^ V. Kouznetsov, Vladímir (2008). "Antimalarials: construction of molecular hybrids based on chloroquine" (PDF). Universitas Scientiarum: 1 – via scielo.
  37. ^ Krafts K, Hempelmann E, Skórska-Stania A (July 2012). "From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy". Parasitology Research. 111 (1): 1–6. doi:10.1007/s00436-012-2886-x. PMID 22411634.
  38. ^ "The History of Malaria, an Ancient Disease". Centers for Disease Control. 29 July 2019. Archived from the original on 28 August 2010.
  39. ^ "Ipca Laboratories: Formulations – Branded".{{cite web}}: CS1 maint: url-status (link)
  40. ^ pubmeddev; MJ, Vincent; Al., Et (18 March 2020). "Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. - PubMed". NCBI. Retrieved 18 March 2020.
  41. ^ "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro - Cell Research". Nature. Retrieved 18 March 2020.
  42. ^ Zhao, Yuning (30 January 2020). "Three drugs fairly effective on novel coronavirus at cellular level". China News Service. Archived from the original on 29 January 2020. Retrieved 1 February 2020.
  43. ^ Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. (February 2020). "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro". Cell Research. 30 (3): 269–271. doi:10.1038/s41422-020-0282-0. PMC 7054408. PMID 32020029.
  44. ^ "Could an old malaria drug help fight the new coronavirus?". asbmb.org. Retrieved 6 February 2020.
  45. ^ Keyaerts, Els; Vijgen, Leen; Maes, Piet; Neyts, Johan; Ranst, Marc Van (8 October 2004). "In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine". Biochemical and Biophysical Research Communications. 323 (1): 264–268. doi:10.1016/j.bbrc.2004.08.085. ISSN 0006-291X. PMID 15351731.
  46. ^ "Antimalarial drug confirmed effective on COVID-19".
  47. ^ Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. (February 2020). "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro". Cell Research. 30 (3): 269–271. doi:10.1038/s41422-020-0282-0. PMC 7054408. PMID 32020029.
  48. ^ multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia (20 February 2020). "[Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia]". Zhonghua Jie He He Hu Xi Za Zhi = Zhonghua Jiehe He Huxi Zazhi = Chinese Journal of Tuberculosis and Respiratory Diseases. 43: E019. doi:10.3760/cma.j.issn.1001-0939.2020.0019. ISSN 1001-0939. PMID 32075365.
  49. ^ 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?". The Lancet. Infectious Diseases. 3 (11): 722–7. doi:10.1016/S1473-3099(03)00806-5. PMID 14592603.
  50. ^ Savarino A, Lucia MB, Giordano F, Cauda R (October 2006). "Risks and benefits of chloroquine use in anticancer strategies". The Lancet. Oncology. 7 (10): 792–3. doi:10.1016/S1470-2045(06)70875-0. PMID 17012039.
  51. ^ Sotelo J, Briceño E, López-González MA (March 2006). "Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial". Annals of Internal Medicine. 144 (5): 337–43. doi:10.7326/0003-4819-144-5-200603070-00008. PMID 16520474.
    "Summaries for patients. Adding chloroquine to conventional chemotherapy and radiotherapy for glioblastoma multiforme". Annals of Internal Medicine. 144 (5): I31. March 2006. doi:10.7326/0003-4819-144-5-200603070-00004. PMID 16520470.
Scholia has a topic profile for Chloroquine.
  • "Chloroquine". Drug Information Portal. U.S. National Library of Medicine.
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