Chloroquine Explained

Watchedfields:changed
Verifiedrevid:459442331
Width:200
Width2:180
Tradename:Aralen, other
Dailymedid:Chloroquine
Routes Of Administration:By mouth
Atc Prefix:P01
Atc Suffix:BA01
Legal Uk:P
Legal Us:Rx-only
Legal Status:Rx only
Metabolism:Liver
Elimination Half-Life:1-2 months
Cas Number:54-05-7
Pubchem:2719
Iuphar Ligand:5535
Drugbank:DB00608
Chemspiderid:2618
Unii:886U3H6UFF
Kegg:D02366
Chebi:3638
Chembl:76
Niaid Chemdb:000733
Synonyms:Chloroquine phosphate
Iupac Name:(RS)-N-(7-chloroquinolin-4-yl)-N,N-diethylpentane-1,4-diamine
C:18
H:26
Cl:1
N:3
Smiles:Clc1cc2nccc(c2cc1)NC(C)CCCN(CC)CC
Stdinchi: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)
Stdinchikey:WHTVZRBIWZFKQO-UHFFFAOYSA-N

Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects.[1] Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication. Chloroquine is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus. While it has not been formally studied in pregnancy, it appears safe.[2] It was studied to treat COVID-19 early in the pandemic, but these studies were largely halted in the summer of 2020, and the NIH does not recommend its use for this purpose.[3] It is taken by mouth.

Common side effects include muscle problems, loss of appetite, diarrhea, and skin rash. Serious side effects include problems with vision, muscle damage, seizures, and low blood cell levels.[4] Chloroquine is a member of the drug class 4-aminoquinoline. As an antimalarial, it works against the asexual form of the malaria parasite in the stage of its life cycle within the red blood cell. How it works in rheumatoid arthritis and lupus erythematosus is unclear.

Chloroquine was discovered in 1934 by Hans Andersag.[5] [6] It is on the World Health Organization's List of Essential Medicines.[7] It is available as a generic medication.

Medical uses

Malaria

Chloroquine has been used in the treatment and prevention of malaria from Plasmodium vivax, P. ovale, and P. malariae. It is generally not used for Plasmodium falciparum as there is widespread resistance to it.[8] [9]

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.[10] 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.[11]

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 five days or intolerance to metronidazole or a nitroimidazole.

Rheumatic disease

As it mildly suppresses the immune system, chloroquine is used in some autoimmune disorders, such as rheumatoid arthritis and has an off-label indication for lupus erythematosus.

Side effects

Side effects include blurred vision, nausea, vomiting, abdominal cramps, headache, diarrhea, swelling legs/ankles, shortness of breath, pale lips/nails/skin, muscle weakness, easy bruising/bleeding, hearing and mental problems.[12] [13]

Pregnancy

Chloroquine has not been shown to have any harmful effects on the fetus when used in the recommended doses for malarial prophylaxis.[19] Small amounts of chloroquine are excreted in the breast milk of lactating women. However, 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.[20] Women who are pregnant or planning on getting pregnant are still advised against traveling to malaria-risk regions.

Elderly

There is not enough evidence to determine whether chloroquine is safe to be given to people aged 65 and older. Since it is cleared by the kidneys, toxicity should be monitored carefully in people with poor kidney functions, as is more likely to be the case in the elderly.

Drug interactions

Chloroquine has a number of drug–drug interactions that might be of clinical concern:

Overdose

Chloroquine, in overdose, has a risk of death of about 20%.[21] It is rapidly absorbed from the gut with an onset of symptoms generally within an hour. Symptoms of overdose may include sleepiness, vision changes, seizures, stopping of breathing, and heart problems such as ventricular fibrillation and low blood pressure.[21] Low blood potassium may also occur.[21]

While the usual dose of chloroquine used in treatment is 10 mg/kg, toxicity begins to occur at 20 mg/kg, and death may occur at 30 mg/kg.[21] In children as little as a single tablet can be fatal.[22] [18]

Treatment recommendations include early mechanical ventilation, cardiac monitoring, and activated charcoal.[21] Intravenous fluids and vasopressors may be required with epinephrine being the vasopressor of choice.[21] Seizures may be treated with benzodiazepines.[21] Intravenous potassium chloride may be required, however this may result in high blood potassium later in the course of the disease.[21] Dialysis has not been found to be useful.[21]

Pharmacology

Absorption of chloroquine is rapid and primarily happens in the gastrointestinal tract.[23] It is widely distributed in body tissues.[24] Protein binding in plasma ranges from 46% to 79%.[25] Its metabolism is partially hepatic, giving rise to its main metabolite, desethylchloroquine.[26] Its excretion is ≥50% as unchanged drug in urine, where acidification of urine increases its elimination. It has a very high volume of distribution, as it diffuses into the body's adipose tissue.

Accumulation of the drug may result in deposits that can lead to blurred vision and blindness.[27] It and related quinines have been associated with cases of retinal toxicity, particularly when provided at higher doses for longer times. 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 pKa for the quinoline nitrogen of chloroquine is 8.5, meaning it is about 10% deprotonated at physiological pH (per 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.

Mechanism of action

Malaria

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,[28] [29] autophagy, and apoptosis.[30]

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.

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.

Chloroquine enters the red blood cell by simple diffusion, inhibiting the parasite cell and digestive vacuole. Chloroquine (CQ) 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.[31] Parasites that do not form hemozoin are therefore resistant to chloroquine.[32]

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.

Resistant parasites are able to rapidly remove chloroquine from the digestive vacuole using a transmembrane pump. Chloroquine-resistant parasites pump chloroquine out at 40 times the rate of chloroquine-sensitive parasites; the pump is coded by the P. falciparum chloroquine resistance transporter (PfCRT) gene.[33] The natural function of the chloroquine pump is to transport peptides: mutations to the pump that allow it to pump chloroquine out impairs its function as a peptide pump and comes at a cost to the parasite, making it less fit.[34]

Resistant parasites also frequently have mutation in the ABC transporter P. falciparum multidrug resistance (PfMDR1) gene, although these mutations are thought to be of secondary importance compared to PfCRT. An altered chloroquine-transporter protein, CG2 has been associated with chloroquine resistance, but other mechanisms of resistance also appear to be involved.[35]

Verapamil, a Ca2+ channel blocker, has been found to restore both the chloroquine concentration ability and sensitivity to this drug. Other agents which have been shown to reverse chloroquine resistance in malaria are chlorpheniramine, gefitinib, imatinib, tariquidar and zosuquidar.[36]

chloroquine is still effective against poultry malaria in Thailand. Sohsuebngarm et al. 2014 test P. gallinaceum at Chulalongkorn University and find the parasite is not resistant.[37] Sertraline, fluoxetine and paroxetine reverse chloroquine resistance, making resistant biotypes susceptible if used in a cotreatment.[38]

Antiviral

Chloroquine has antiviral effects against some viruses.[39] It increases late endosomal and lysosomal pH, resulting in impaired release of the virus from the endosome or lysosome — release of the virus requires a low pH. The virus is therefore unable to release its genetic material into the cell and replicate.[40] [41]

Chloroquine also seems to act as a zinc ionophore that allows extracellular zinc to enter the cell and inhibit viral RNA-dependent RNA polymerase.[42] [43]

Other

Chloroquine inhibits thiamine uptake.[44] 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

In Peru, the indigenous people extracted the bark of the Cinchona tree (Cinchona officinalis)[45] and used the extract 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. The quinoline antimalarial drug quinine was isolated from the extract in 1820.[46]

After World War I, the German government sought alternatives to quinine. Chloroquine, a synthetic analogue with the same mechanism of action was discovered in 1934, by Hans Andersag and coworkers at the Bayer laboratories, who named it Resochin.[47] [48] It was ignored for a decade, because it was considered too toxic for human use. Instead, in World War II, the German Africa Corps used the chloroquine analogue 3-methyl-chloroquine, known as Sontochin. After Allied forces arrived in Tunis, Sontochin fell into the hands of Americans, who sent the material back to the United States for analysis, leading to renewed interest in chloroquine.[49] [50] 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.[51]

Chemical synthesis

The first synthesis of chloroquine was disclosed in a patent filed by IG Farben in 1937.[52] In the final step, 4,7-dichloroquinoline was reacted with 1-diethylamino-4-aminopentane.

By 1949, chloroquine manufacturing processes had been established to allow its widespread use.[53]

Society and culture

Formulations

Chloroquine comes in tablet form as the phosphate, sulfate, and hydrochloride salts. Chloroquine is usually dispensed as the phosphate.[54]

Names

Brand names include Chloroquine FNA, Resochin, Dawaquin, and Lariago.[55]

Other animals

Chloroquine, in various chemical forms, is used to treat and control surface growth of anemones and algae, and many protozoan infections in aquariums,[56] e.g. the fish parasite Amyloodinium ocellatum.[57] It is also used in poultry malaria.

Research

Chloroquine was proposed as a treatment for SARS, with in vitro tests inhibiting the severe acute respiratory syndrome coronavirus (SARS-CoV).[58] [59] In October 2004, a published report stated that chloroquine acts as an effective inhibitor of the replication of SARS-CoV in vitro.[58] In August 2005, a peer-reviewed study confirmed and expanded upon the results.[60]

Chloroquine was being considered in 2003, in pre-clinical models as a potential agent against chikungunya fever.[61]

Other

The radiosensitizing and chemosensitizing properties of chloroquine are being evaluated for anticancer strategies in humans.[62] [63] In biomedicinal science, chloroquine is used for in vitro experiments to inhibit lysosomal degradation of protein products. Chloroquine and its modified forms have also been evaluated as treatment options for inflammatory conditions like rheumatoid arthritis and inflammatory bowel disease.[64]

External links

Notes and References

  1. Web site: Aralen Phosphate. The American Society of Health-System Pharmacists. 2 December 2015. live. https://web.archive.org/web/20151208200339/http://www.drugs.com/monograph/aralen-phosphate.html. 8 December 2015.
  2. Web site: Chloroquine Use During Pregnancy . Drugs.com . 16 April 2019 . There are no controlled data in human pregnancies. . https://web.archive.org/web/20190416201619/https://www.drugs.com/pregnancy/chloroquine.html . 16 April 2019 . live .
  3. Web site: Chloroquine or Hydroxychloroquine. live. https://web.archive.org/web/20200828170647/https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/chloroquine-or-hydroxychloroquine-with-or-without-azithromycin/ . 28 August 2020 . 14 February 2021. COVID-19 Treatment Guidelines. National Institutes of Health. en.
  4. Book: Mittra RA, Mieler WG . Retina . Fifth . 2013 . W.B. Saunders . 978-1-4557-0737-9 . 1532–1554 . 10.1016/B978-1-4557-0737-9.00089-8 . 25 March 2020 . en . Chapter 89 – Drug Toxicity of the Posterior Segment . https://entokey.com/drug-toxicity-of-the-posterior-segment/ .
  5. Book: Manson P, Cooke G, Zumla A . Manson's tropical diseases. . 2009 . Saunders . [Edinburgh] . 978-1-4160-4470-3 . 1240 . 22nd . 9 September 2017 . https://web.archive.org/web/20181102004125/https://books.google.com/books?id=CF2INI0O6l0C&pg=PA1240 . 2 November 2018 . live .
  6. Book: Bhattacharjee M . Chemistry of Antibiotics and Related Drugs . 2016 . Springer . 978-3-319-40746-3 . 184 . 9 September 2017 . https://web.archive.org/web/20181101204139/https://books.google.com/books?id=vgXWDAAAQBAJ&pg=PA184 . 1 November 2018 . live .
  7. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. free .
  8. Book: Plowe CV . Malaria: Drugs, Disease and Post-genomic Biology . Antimalarial drug resistance in Africa: strategies for monitoring and deterrence . 295 . 55–79 . 2005 . 16265887 . 10.1007/3-540-29088-5_3 . https://archive.org/details/malariadrugsdise0000unse/page/55 . 3-540-25363-7 . Current Topics in Microbiology and Immunology . Springer .
  9. Book: 10.1007/3-540-29088-5_2 . Antimalarial Multi-Drug Resistance in Asia: Mechanisms and Assessment . Malaria: Drugs, Disease and Post-genomic Biology . Current Topics in Microbiology and Immunology . 2005 . Uhlemann AC, Krishna S . 295 . 39–53 . Springer . 16265886 . 978-3-540-25363-1 .
  10. Web site: Chloroquine phosphate tablet – chloroquine phosphate tablet, coated. dailymed.nlm.nih.gov. 4 November 2015. live. https://web.archive.org/web/20151208164343/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9b585ad5-ae86-4403-b83f-8d8363d43da5. 8 December 2015.
  11. CDC. Health information for international travel 2001–2002. Atlanta, Georgia: U.S. Department of Health and Human Services, Public Health Service, 2001.
  12. Web site: Drugs & Medications. www.webmd.com. 22 March 2020.
  13. Web site: Chloroquine Side Effects: Common, Severe, Long Term. Drugs.com. 22 March 2020.
  14. Web site: Chloroquine: MedlinePlus Drug Information. medlineplus.gov. 22 March 2020.
  15. Ajayi AA . Mechanisms of chloroquine-induced pruritus . Clinical Pharmacology and Therapeutics . 68 . 3 . 336 . September 2000 . 11014416 .
  16. Vaziri A, Warburton B . Slow release of chloroquine phosphate from multiple taste-masked W/O/W multiple emulsions . Journal of Microencapsulation . 11 . 6 . 641–648 . 1994 . 7884629 . 10.3109/02652049409051114 .
  17. Tönnesmann E, Kandolf R, Lewalter T . Chloroquine cardiomyopathy - a review of the literature . Immunopharmacology and Immunotoxicology . 35 . 3 . 434–442 . June 2013 . 23635029 . 10.3109/08923973.2013.780078 . 37926477 .
  18. Web site: Chloroquine phosphate tablet . DailyMed . 8 October 2018 . 7 April 2020.
  19. Web site: Malaria – Chapter 3 – 2016 Yellow Book . wwwnc.cdc.gov. 11 November 2015. live. https://web.archive.org/web/20160114185552/http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/malaria. 14 January 2016.
  20. Ullberg S, Lindquist NG, Sjòstrand SE . Accumulation of chorio-retinotoxic drugs in the foetal eye . Nature . 227 . 5264 . 1257–1258 . September 1970 . 5452818 . 10.1038/2271257a0 . 4191322 . 1970Natur.227.1257U .
  21. Ling Ngan Wong A, Tsz Fung Cheung I, Graham CA . Hydroxychloroquine overdose: case report and recommendations for management . European Journal of Emergency Medicine . 15 . 1 . 16–18 . February 2008 . 18180661 . 10.1097/MEJ.0b013e3280adcb56 . 41205035 .
  22. Smith ER, Klein-Schwartz W . Are 1-2 dangerous? Chloroquine and hydroxychloroquine exposure in toddlers . The Journal of Emergency Medicine . 28 . 4 . 437–443 . May 2005 . 15837026 . 10.1016/j.jemermed.2004.12.011 .
  23. Web site: Chloroquine . §6.1 Absorption by route of exposure . 24 April 2020.
  24. Adelusi SA, Salako LA . Tissue and blood concentrations of chloroquine following chronic administration in the rat . The Journal of Pharmacy and Pharmacology . 34 . 11 . 733–735 . November 1982 . 6129306 . 10.1111/j.2042-7158.1982.tb06211.x . 35269419 .
  25. Walker O, Birkett DJ, Alván G, Gustafsson LL, Sjöqvist F . Characterization of chloroquine plasma protein binding in man . British Journal of Clinical Pharmacology . 15 . 3 . 375–377 . March 1983 . 6849768 . 1427768 . 10.1111/j.1365-2125.1983.tb01513.x . free .
  26. Projean D, Baune B, Farinotti R, Flinois JP, Beaune P, Taburet AM, Ducharme J . In vitro metabolism of chloroquine: identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation . Drug Metabolism and Disposition . 31 . 6 . 748–754 . June 2003 . 12756207 . 10.1124/dmd.31.6.748 . 2115928 .
  27. Handzel DM, Romanou-Papadopoulou V, Briesen S . [Visual loss under chloroquine treatment-and not (only) due to bull's eye maculopathy!] . German . Der Ophthalmologe . 118 . 9 . 953–955 . September 2021 . 33300096 . 10.1007/s00347-020-01288-y . 228089310 . Visual loss under chloroquine treatment-and not (only) due to bull's eye maculopathy! .
  28. Chen PM, Gombart ZJ, Chen JW . 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 . March 2011 . 21711726 . 3125200 . 10.1186/2045-3701-1-10 . free .
  29. Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, Nairn AC, Lombroso PJ . Abeta-mediated NMDA receptor endocytosis in Alzheimer's disease involves ubiquitination of the tyrosine phosphatase STEP61 . The Journal of Neuroscience . 30 . 17 . 5948–5957 . April 2010 . 20427654 . 2868326 . 10.1523/JNEUROSCI.0157-10.2010 .
  30. Kim EL, Wüstenberg R, Rübsam A, Schmitz-Salue C, Warnecke G, Bücker EM, Pettkus N, Speidel D, Rohde V, Schulz-Schaeffer W, Deppert W, Giese A . Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells . Neuro-Oncology . 12 . 4 . 389–400 . April 2010 . 20308316 . 2940600 . 10.1093/neuonc/nop046 .
  31. Hempelmann E . Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors . Parasitology Research . 100 . 4 . 671–676 . March 2007 . 17111179 . 10.1007/s00436-006-0313-x . 30446678 .
  32. 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 . Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance . The Journal of Experimental Medicine . 212 . 6 . 893–903 . June 2015 . 25941254 . 4451122 . 10.1084/jem.20141731 . 4 November 2018 . live . https://web.archive.org/web/20170922103013/https://lirias.kuleuven.be/bitstream/123456789/500975/3/2015113.pdf . 22 September 2017 .
  33. Martin RE, Marchetti RV, Cowan AI, Howitt SM, Bröer S, Kirk K . Chloroquine transport via the malaria parasite's chloroquine resistance transporter . Science . 325 . 5948 . 1680–1682 . September 2009 . 19779197 . 10.1126/science.1175667 . 206520905 . 2009Sci...325.1680M .
  34. Shafik SH, Cobbold SA, Barkat K, Richards SN, Lancaster NS, Llinás M, Hogg SJ, Summers RL, McConville MJ, Martin RE . The natural function of the malaria parasite's chloroquine resistance transporter . Nature Communications . 11 . 1 . 3922 . August 2020 . 32764664 . 7413254 . 10.1038/s41467-020-17781-6 . 2020NatCo..11.3922S .
  35. Book: Tripathi KD . Essentials of Medical Pharmacology . fifth . 2003 . Jaypee Brothers Medical Publisher Ltd . 739–740 .
  36. Alcantara LM, Kim J, Moraes CB, Franco CH, Franzoi KD, Lee S, Freitas-Junior LH, Ayong LS . Chemosensitization potential of P-glycoprotein inhibitors in malaria parasites . Experimental Parasitology . 134 . 2 . 235–243 . June 2013 . 23541983 . 10.1016/j.exppara.2013.03.022 .
  37. Book: McDougald LR, Cervantes HM, Jenkins MC, Hess M, Beckstead R . Diseases of Poultry . 14 . Protozoal Infections . . 22 November 2019 . 9781119371199.
  38. Munoz-Bellido JL, Munoz-Criado S, Garcìa-Rodrìguez JA . Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors . International Journal of Antimicrobial Agents . 14 . 3 . 177–180 . April 2000 . 10773485 . 10.1016/s0924-8579(99)00154-5 . International Society of Chemotherapy (Elsevier) .
  39. Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R . Effects of chloroquine on viral infections: an old drug against today's diseases? . The Lancet. Infectious Diseases . 3 . 11 . 722–727 . November 2003 . 14592603 . 7128816 . 10.1016/s1473-3099(03)00806-5 .
  40. Al-Bari MA . Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases . Pharmacology Research & Perspectives . 5 . 1 . e00293 . February 2017 . 28596841 . 5461643 . 10.1002/prp2.293 .
  41. Fredericksen BL, Wei BL, Yao J, Luo T, Garcia JV . Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus . Journal of Virology . 76 . 22 . 11440–11446 . November 2002 . 12388705 . 136743 . 10.1128/JVI.76.22.11440-11446.2002 .
  42. Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ . Chloroquine is a zinc ionophore . PLOS ONE . 9 . 10 . e109180 . 1 October 2014 . 25271834 . 4182877 . 10.1371/journal.pone.0109180 . free . 2014PLoSO...9j9180X .
  43. te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ . Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture . PLOS Pathogens . 6 . 11 . e1001176 . November 2010 . 21079686 . 2973827 . 10.1371/journal.ppat.1001176 . free .
  44. Huang Z, Srinivasan S, Zhang J, Chen K, Li Y, Li W, Quiocho FA, Pan X . Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy . PLOS Genetics . 8 . 11 . e1003083 . 2012 . 23209439 . 3510038 . 10.1371/journal.pgen.1003083 . free .
  45. Web site: Cinchona officinalis – L.. Fern K . 2010–2020. Plans for a Future. live. https://web.archive.org/web/20170825212410/http://www.pfaf.org/user/Plant.aspx?LatinName=Cinchona+officinalis . 25 August 2017. 2 February 2020.
  46. Book: 9780309092180 . 10.17226/11017. free. Arrow KJ, Panosian C, Gelband H . Saving lives, buying time : economics of malaria drugs in an age of resistance. 2004. National Academies Press. 25009879. Institute of Medicine (US) Committee on the Economics of Antimalarial Drug.
  47. Kouznetsov VV, Amado Torres DF . Antimalarials: construction of molecular hybrids based on chloroquine . Universitas Scientiarum . September 2008 . 13 . 3 . 306–320 .
  48. Krafts K, Hempelmann E, Skórska-Stania A . From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy . Parasitology Research . 111 . 1 . 1–6 . July 2012 . 22411634 . 10.1007/s00436-012-2886-x . 54526057 .
  49. Book: Sneader W . Drug Discovery. A History. . Wiley . 2005 . 0471899801.
  50. Pou S, Winter RW, Nilsen A, Kelly JX, Li Y, Doggett JS, Riscoe EW, Wegmann KW, Hinrichs DJ, Riscoe MK . Sontochin as a guide to the development of drugs against chloroquine-resistant malaria . Antimicrobial Agents and Chemotherapy . 56 . 7 . 3475–3480 . July 2012 . 22508305 . 3393441 . 10.1128/AAC.00100-12 . 32186437 .
  51. Web site: The History of Malaria, an Ancient Disease . Centers for Disease Control . live . https://web.archive.org/web/20100828183012/http://www.cdc.gov//malaria//history//index.htm#chloroquine . 28 August 2010. 29 July 2019 .
  52. DE . 683692 . patent . 1939-11-13 . 1937-10-08 . 1937-10-08 . Andersag, Hans . Breitner, Stefan . Jung, Heinrich . Process for the preparation of quinoline compounds containing amino groups with basic substituents in the 4-position . IG Farbenindustrie AG.
  53. 10.1021/ie50472a002. Kenyon RL, Wiesner JA, Kwartler CE . Chloroquine manufacture. 1 April 1949. Industrial & Engineering Chemistry. 41. 4. 654–662 .
  54. Web site: Chloroquine . nih.gov . National Institutes of Health . 24 March 2020.
  55. Web site: Ipca Laboratories: Formulations – Branded. live. https://web.archive.org/web/20190406132110/https://ipca.com/pharmaceutical-formulations-manufacturers-india.html. 6 April 2019. 14 March 2020.
  56. Web site: Aquarium Fish: Chloroquine: A "New" Drug for Treating Fish Diseases . Hemdal J . 26 March 2020 . Advanced Aquarist . 20 February 2013 . XII . live . https://web.archive.org/web/20130315115122/https://www.advancedaquarist.com/2013/2/fish . 15 March 2013.
  57. Web site: Francis-Floyd R, Floyd MR . Amyloodinium ocellatum, an Important Parasite of Cultured Marine Fish . agrilife.org . 24 March 2020 . https://web.archive.org/web/20150601235926/http://agrilife.org/fisheries/files/2013/09/SRAC-Publication-No.-4705-Amyloodinium-ocellatum-an-Important-Parasite-of-Cultured-Marine-Fish.pdf . 1 June 2015 . dead .
  58. Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M . In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine . Biochemical and Biophysical Research Communications . 323 . 1 . 264–268 . October 2004 . 15351731 . 7092815 . 10.1016/j.bbrc.2004.08.085 .
  59. Devaux CA, Rolain JM, Colson P, Raoult D . New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? . International Journal of Antimicrobial Agents . 55 . 5 . 105938 . May 2020 . 32171740 . 7118659 . 10.1016/j.ijantimicag.2020.105938 .
  60. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST . Chloroquine is a potent inhibitor of SARS coronavirus infection and spread . Virology Journal . 2 . 69 . August 2005 . 16115318 . 1232869 . 10.1186/1743-422X-2-69 . free .
  61. Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R . Effects of chloroquine on viral infections: an old drug against today's diseases? . The Lancet. Infectious Diseases . 3 . 11 . 722–727 . November 2003 . 14592603 . 7128816 . 10.1016/S1473-3099(03)00806-5 .
  62. Savarino A, Lucia MB, Giordano F, Cauda R . Risks and benefits of chloroquine use in anticancer strategies . The Lancet. Oncology . 7 . 10 . 792–793 . October 2006 . 17012039 . 10.1016/S1470-2045(06)70875-0 .
  63. Sotelo J, Briceño E, López-González MA . Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial . Annals of Internal Medicine . 144 . 5 . 337–343 . March 2006 . 16520474 . 10.7326/0003-4819-144-5-200603070-00008 . 24807955 .
    Summaries for patients. Adding chloroquine to conventional chemotherapy and radiotherapy for glioblastoma multiforme . Annals of Internal Medicine . 144 . 5 . I31 . March 2006 . 16520470 . 10.7326/0003-4819-144-5-200603070-00004 . free .
  64. Book: Goel P, Gerriets V . Chloroquine . StatPearls . Treasure Island (FL) . StatPearls Publishing LLC. . January 2020 . 31855356 . https://www.ncbi.nlm.nih.gov/books/NBK551512/ .

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