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Details

Stereochemistry RACEMIC
Molecular Formula C18H26ClN3.H3O4P
Molecular Weight 417.867
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CHLOROQUINE MONOPHOSPHATE

SMILES

OP(O)(O)=O.CCN(CC)CCCC(C)NC1=CC=NC2=C1C=CC(Cl)=C2

InChI

InChIKey=AEUAEICGCMSYCQ-UHFFFAOYSA-N
InChI=1S/C18H26ClN3.H3O4P/c1-4-22(5-2)12-6-7-14(3)21-17-10-11-20-18-13-15(19)8-9-16(17)18;1-5(2,3)4/h8-11,13-14H,4-7,12H2,1-3H3,(H,20,21);(H3,1,2,3,4)

HIDE SMILES / InChI
Chloroquine (brand name Aralen) is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. In addition, chloroquine is in clinical trials as an investigational antiretroviral in humans with HIV-1/AIDS and as a potential antiviral agent against chikungunya fever. The mechanism of plasmodicidal action of chloroquine is not completely certain. However, is existed theory, that like other quinoline derivatives, it is thought to inhibit heme polymerase activity. 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. 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.

CNS Activity

Curator's Comment: Known to be CNS penetrant in rat. Human data not available.

Originator

Curator's Comment: # Hans Andersag and coworkers at the Bayer laboratories

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
ARALEN

Approved Use

ARALEN is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. ARALEN does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.

Launch Date

1949
Curative
ARALEN

Approved Use

ARALEN is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. ARALEN does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.

Launch Date

1949
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
700 ng/mL
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CHLOROQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
134087 ng × h/mL
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CHLOROQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
209 h
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CHLOROQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
45%
5 mg/kg 1 times / day multiple, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CHLOROQUINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3 g single, oral
Overdose
Dose: 3 g
Route: oral
Route: single
Dose: 3 g
Sources:
unknown, 14 years
n = 1
Health Status: unknown
Age Group: 14 years
Sex: F
Population Size: 1
Sources:
Other AEs: Cardiac arrest...
Other AEs:
Cardiac arrest
Sources:
600 mg 2 times / day multiple, oral (starting)
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
n = 300
Health Status: pregnant
Condition: malaria
Age Group: 20.7 years
Sex: F
Population Size: 300
Sources:
Other AEs: Dizziness, Vomiting...
Other AEs:
Dizziness (19%)
Vomiting (17%)
Palpitations (5%)
Headache (6%)
Nausea (5%)
Abdominal pain (2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Cardiac arrest
3 g single, oral
Overdose
Dose: 3 g
Route: oral
Route: single
Dose: 3 g
Sources:
unknown, 14 years
n = 1
Health Status: unknown
Age Group: 14 years
Sex: F
Population Size: 1
Sources:
Vomiting 17%
600 mg 2 times / day multiple, oral (starting)
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
n = 300
Health Status: pregnant
Condition: malaria
Age Group: 20.7 years
Sex: F
Population Size: 300
Sources:
Dizziness 19%
600 mg 2 times / day multiple, oral (starting)
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
n = 300
Health Status: pregnant
Condition: malaria
Age Group: 20.7 years
Sex: F
Population Size: 300
Sources:
Abdominal pain 2%
600 mg 2 times / day multiple, oral (starting)
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
n = 300
Health Status: pregnant
Condition: malaria
Age Group: 20.7 years
Sex: F
Population Size: 300
Sources:
Nausea 5%
600 mg 2 times / day multiple, oral (starting)
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
n = 300
Health Status: pregnant
Condition: malaria
Age Group: 20.7 years
Sex: F
Population Size: 300
Sources:
Palpitations 5%
600 mg 2 times / day multiple, oral (starting)
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
n = 300
Health Status: pregnant
Condition: malaria
Age Group: 20.7 years
Sex: F
Population Size: 300
Sources:
Headache 6%
600 mg 2 times / day multiple, oral (starting)
Highest studied dose
Dose: 600 mg, 2 times / day
Route: oral
Route: multiple
Dose: 600 mg, 2 times / day
Sources:
pregnant, 20.7 years
n = 300
Health Status: pregnant
Condition: malaria
Age Group: 20.7 years
Sex: F
Population Size: 300
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no (co-administration study)
Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4
no
no (co-administration study)
Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4
no
no (co-administration study)
Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4
no
no (co-administration study)
Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4
yes [IC50 1096 uM]
yes [IC50 2.5 uM]
yes [Ki 12 uM]
weak (co-administration study)
Comment: selective inhibiton; Chloroquine produced a reduction in the metabolism of debrisoquine as evaluated by the debrisoquine recovery ratio, a measure of CYP2D6 activity. This reduction was progressive from the first to the seventh dose. This decrease in metabolism was modest (about 7% after the first dose and about 18% after seven doses) but statistically significant
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes (co-administration study)
Comment: Concomitant administration of a single dose of chloroquine and cimetidine daily starting 4 days prior to chloroquine, resulted in a 50% increase in chloroquine half-life, associated with a 50% decrease in its clearance.Since the AUC of desethylchloroquine decreased by 47%, cimetidine probably decreased chloroquine clearance by inhibiting its hepatic desethylation.
yes
yes (co-administration study)
Comment: Concomitant administration of a single dose of chloroquine and cimetidine daily starting 4 days prior to chloroquine, resulted in a 50% increase in chloroquine half-life, associated with a 50% decrease in its clearance.Since the AUC of desethylchloroquine decreased by 47%, cimetidine probably decreased chloroquine clearance by inhibiting its hepatic desethylation.
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
A Comparative Study of Hymenolepicides in Hymenolepis Mana Infestation of Rats.
1962 Jul
Amrinone for refractory cardiogenic shock following chloroquine poisoning.
1991
Occurrence of chloroquine-induced psychotic manifestations in children with malaria.
1992
Seizures associated with chloroquine therapy.
1992 Aug
Chloroquine related complete heart block with blindness: case report.
1992 Jan
Involvement of GABAergic mechanisms in chloroquine-induced seizures in mice.
1992 Mar
[Heart conduction disorders in long-term treatment with chloroquine. Two new cases].
1992 May 2-9
Cardiac damage from chronic use of chloroquine: a case report and review of the literature.
2002 Jul
Side effects of and compliance with malaria prophylaxis in children.
2002 Nov-Dec
[Chloroquine cardiomyopathy revealed by complete atrio-ventricular block. A case report].
2002 Sep
EGb 761 is a neuroprotective agent against beta-amyloid toxicity.
2002 Sep
Control of mammary tumor cell growth in vitro by novel cell differentiation and apoptosis agents.
2002 Sep
Chloroquine cardiotoxicity: clinicopathologic features in three patients and comparison with three patients with Fabry disease.
2002 Sep-Oct
Severe mucocutaneous necrotizing vasculitis associated with the combination of chloroquine and proguanil.
2003
Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine.
2003 Feb 15
[Toxic lesions of the organ of vision caused by chloroquine derivatives].
2003 Jan-Feb
Chloroquine-induced phospholipidosis of the kidney mimicking Fabry's disease: case report and review of the literature.
2003 Mar
[Chloroquine-induced myopathy and neuropathy: progressive tetraparesis with areflexia that simulates a polyradiculoneuropathy. Two case reports].
2003 Mar 16-31
Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus.
2003 Nov
Increased CSF protein in chloroquine-induced axonal polyneuropathy and myopathy.
2003 Sep
Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data.
2003 Sep
[Infectious diseases in 2003].
2004
Heart transplantation in a patient with chloroquine-induced cardiomyopathy.
2004 Feb
The antimalarial potential of 4-quinolinecarbinolamines may be limited due to neurotoxicity and cross-resistance in mefloquine-resistant Plasmodium falciparum strains.
2004 Jul
Survival and surface adherence ability of bacterial pathogens in oral liquid pharmaceuticals and their containers.
2004 Jun
Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract.
2004 Jun 11
The multifocal pattern electroretinogram in chloroquine retinopathy.
2004 Mar-Apr
The ability of chloroquine to prevent tat-induced cytokine secretion by monocytes is implicated in its in vivo anti-human immunodeficiency virus type 1 activity.
2004 Nov
Seizure associated with chloroquine therapy in a patient with systemic lupus erythematosus.
2004 Sep
Chloroquine-induced cardiomyopathy-echocardiographic features.
2005 Apr
Skeletal muscle expression of clathrin and mannose 6-phosphate receptor in experimental chloroquine-induced myopathy.
2005 Apr
Enhanced anticryptococcal activity of chloroquine in phosphatidylserine-containing liposomes in a murine model.
2005 Feb
[Malaria chemoprophylaxis in traveling children].
2005 Jan
[Acute hydroxychloroquine poisoning. The danger of rapid or excessive correction of initial hypokalemia].
2005 Jul 23
Chloroquine-induced lipidosis mimicking Fabry disease.
2005 May
Protective effects of different antioxidants and amrinone on vancomycin-induced nephrotoxicity.
2005 Nov
Selective enhancement of cellular oxidative stress by chloroquine: implications for the treatment of glioblastoma multiforme.
2006 Dec 15
CpG-B oligodeoxynucleotide promotes cell survival via up-regulation of Hsp70 to increase Bcl-xL and to decrease apoptosis-inducing factor translocation.
2006 Dec 15
[Cytochrome P-450 and the response to antimalarial drugs].
2006 Jan
Plasmodium berghei: development of an irreversible experimental malaria model in Wistar rats.
2006 Jul
Mefloquine toxicity presenting with polyneuropathy - a report of two cases in India.
2006 Jun
Frequency of high-risk use of QT-prolonging medications.
2006 Jun
Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients.
2006 Mar
Tetrahydrocurcumin: effect on chloroquine-mediated oxidative damage in rat kidney.
2006 Nov
Cardiomyopathy related to antimalarial therapy with illustrative case report.
2007
Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3.
2007 Jan 9
Chloroquine-induced recurrent psychosis.
2007 Jul-Aug
[Reversible restrictive cardiomyopathy secondary to chloroquine].
2007 Jun 23
Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases.
2007 May
Effects of CpG-B ODN on the protein expression profile of swine PBMC.
2007 Nov-Dec
Patents

Sample Use Guides

The dosage of chloroquine phosphate is often expressed in terms of equivalent chloroquine base. Each 500 mg tablet of ARALEN (chloroquine phosphate) contains the equivalent of 300 mg chloroquine base. In infants and children the dosage is preferably calculated by body weight. Malaria: Suppression—Adult Dose: 500 mg (= 300 mg base) on exactly the same day of each week. Pediatric Dose: The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight. If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this in adults, an initial double (loading) dose of 1 g (= 600 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area. For Treatment of Acute Attack. Adults: An initial dose of 1 g (=600 mg base) followed by an additional 500 mg (= 300 mg base) after six to eight hours and a single dose of 500 mg (= 300 mg base) on each of two consecutive days. This represents a total dose of 2.5 g chloroquine phosphate or 1.5 g base in three days. The dosage for adults of low body weight and for infants and children should be determined as follows: First dose: 10 mg base per kg (but not exceeding a single dose of 600 mg base) Second dose: (6 hours after first dose) 5 mg base per kg (but not exceeding a single dose of 300 mg base) Third dose: (24 hours after first dose) 5mg base per kg Fourth dose: (36 hours after first dose) 5 mg base per kg For radical cure of vivax and malariae malaria concomitant therapy with an 8-aminoquinoline compound is necessary. Extraintestinal Amebiasis: Adults, 1 g (600 mg base) daily for two days, followed by 500 mg (300 mg base) daily for at least two to three weeks. Treatment is usually combined with an effective intestinal amebicide.
Route of Administration: Oral
Chloroquine inhibited mouse colon cancer cell line CT26 cells proliferation by concentration- and time-dependent manner. This effect was associated with apoptosis induction and decreased level of phosphorylated p42/44 mitogen-activated protein kinase and phosphorylated Akt. The cytotoxicity of chloroquine on CT26 cells was determined by the MTT assay. Cells were seeded in 96-well plates at the density of 2000/well and cultured for 24 hr, followed by chloroquine treatment (100, 50, 25, 12.5, 6.25, and 3.125 μ mol/L) for 24, 48, and 72 hr, respectively.
Name Type Language
CHLOROQUINE MONOPHOSPHATE
WHO-DD  
Common Name English
Chloroquine monophosphate [WHO-DD]
Common Name English
Code System Code Type Description
CAS
1446-17-9
Created by admin on Fri Dec 15 15:05:06 GMT 2023 , Edited by admin on Fri Dec 15 15:05:06 GMT 2023
PRIMARY
PUBCHEM
83818
Created by admin on Fri Dec 15 15:05:06 GMT 2023 , Edited by admin on Fri Dec 15 15:05:06 GMT 2023
PRIMARY
FDA UNII
7FY24HE2G3
Created by admin on Fri Dec 15 15:05:06 GMT 2023 , Edited by admin on Fri Dec 15 15:05:06 GMT 2023
PRIMARY
EPA CompTox
DTXSID10932343
Created by admin on Fri Dec 15 15:05:06 GMT 2023 , Edited by admin on Fri Dec 15 15:05:06 GMT 2023
PRIMARY