QuickView for Chloroquine (compound)

Summary
General Info

PubChem

PubChem Compound 10087451

Name:	Chloroquine
PubChem Compound ID:	10087451
Description:	The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.
Molecular formula:	C₁₈H₂₆ClN₃
Molecular weight:	321.88 g/mol

DrugBank

Identification

Name:	Chloroquine
Name (isomeric):	DB00608
Drug Type:	small molecule
Description:	The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.
Synonyms:	Chlorochine; Chloroquina; Chloroquinium; Hydroxychloroquine Sulfate; Chloraquine; Clorochina; Chlorquin; Chloroquine Phosphate
Brand:	Arechin, Avlochlor, Reumaquin, Bemaco, Trochin, Aralen HCl, Resochin, Bemaphate, Tresochin, Silbesan, Malaquin, Resochen, Iroquine, Pfizerquine, Plaquenil, Reumachlor, Aralen, Benaquin, Chlorochin, Lapaquin, Solprina, Cocartrit, Klorokin, Quinilon, Dichinalex, Chemochin, Tanakan, Bipiquin, Quinagamin, Chingamin, Resoquina, Resoquine, 3377 RP opalate, Mesylith, Avloclor, Imagon, Elestol, Delagil, Heliopar, Quinachlor, Siragan, Arthrochin, Quinercyl, Nivaquine, Roquine, Amokin, Quinoscan, Nivachine, Cidanchin, Malaren, Quinagamine, Sopaquin, Malarex, Artrichin, Sanoquin, Nivaquine B, Capquin, Gontochin, Bemasulph, Neochin, Quingamine
Category:	Antimalarials, Amebicides, Antirheumatic Agents
CAS number:	54-05-7

Pharmacology

Indication:	For the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum, Second-line agent in treatment of Rheumatoid Arthritis
Pharmacology:	Chloroquine is the prototype anti malarial drug, most widely used to treat all types of malaria except for disease caused by chloroquine resistant Plasmodium falciparum. It is highly effective against erythrocytic forms of Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, sensitive strains of Plasmodium falc... show more » Chloroquine is the prototype anti malarial drug, most widely used to treat all types of malaria except for disease caused by chloroquine resistant Plasmodium falciparum. It is highly effective against erythrocytic forms of Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, sensitive strains of Plasmodium falciparum and gametocytes of Plasmodium vivax. Being alkaline, the drug reaches high concentration within the food vacuoles of the parasite and raises its pH. It is found to induce rapid clumping of the pigment. Chloroquine inhibits the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. It may also interfere with the biosynthesis of nucleic acids. show less «
Mechanism of Action:	The mechanism of plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. nside red blood cells, the malarial parasite must degrade hemoglobin to acquire essential amino acids, which... show more » The mechanism of plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. nside 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 parasite cell. During this process, the parasite produces 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 non-toxic 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 what is known as 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. show less «
Absorption:	Completely absorbed from gastrointestinal tract
Protein binding:	~55% of the drug in the plasma is bound to nondiffusible plasma constituents
Biotransformation:	Hepatic (partially)
Route of elimination:	Excretion of chloroquine is quite slow, but is increased by acidification of the urine.
Half Life:	1-2 months
Affected organisms:	Plasmodium

Interactions

Food interaction:

Take with food to reduce irritation and increase bioavailability.

Drug interaction:

Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Tamsulosin	Chloroquine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chloroquine is initiated, discontinued, or dose changed.
Aluminium	The antiacid decreases the absorption of chloroquine
Atomoxetine	The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Magnesium oxide	The antiacid decreases the absorption of chloroquine

Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Tamsulosin	Chloroquine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Chloroquine is initiated, discontinued, or dose changed.
Aluminium	The antiacid decreases the absorption of chloroquine
Atomoxetine	The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Magnesium oxide	The antiacid decreases the absorption of chloroquine
Lumefantrine	Chloroquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
Tamoxifen	Chloroquine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Attapulgite	The antiacid decreases the absorption of chloroquine
Kaolin	The antiacid decreases the absorption of chloroquine
Dihydroxyaluminium	The antiacid decreases the absorption of chloroquine
Praziquantel	Markedly lower praziquantel levels
Tramadol	Chloroquine may decrease the effect of Tramadol by decreasing active metabolite production.
Terbinafine	Terbinafine may reduce the metabolism and clearance of Chloroquine. Consider alternate therapy or monitor for therapeutic/adverse effects of Chloroquine if Terbinafine is initiated, discontinued or dose changed.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of chloroquine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of chloroquine if voriconazole is initiated, discontinued or dose changed.
Calcium	The antiacid decreases the absorption of chloroquine
Magnesium	The antiacid decreases the absorption of chloroquine
Artemether	Chloroquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Cyclosporine	Chloroquine may increase the therapeutic and adverse effects of cyclosporine.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Telithromycin	Telithromycin may reduce clearance of Chloroquine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Chloroquine if Telithromycin is initiated, discontinued or dose changed.

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Targets

Ferriprotoporphyrin IX

Glutathione S-transferase A2

Tumor necrosis factor

Enzymes

Transporters

Multidrug resistance protein 1