U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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

Molecular Formula C18H26ClN3
Molecular Weight 319.872
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula H3O4P
Molecular Weight 97.9952
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Nivaquine and urethral pain.
1976 Dec
Tissue and blood concentrations of chloroquine following chronic administration in the rat.
1982 Nov
Kinetics of the uptake and elimination of chloroquine in children with malaria.
1982 Oct
Drug-induced haemolysis and renal failure in children with glucose-6-phosphate dehydrogenase deficiency in Central Asia.
1990
[Heart conduction disorders in long-term treatment with chloroquine. Two new cases].
1992 May 2-9
Calcitriol-mediated hypercalcaemia and increased interleukins in a patient with sarcoid myopathy.
1999
Potential inhibitors of HIV integrase.
1999 Apr-May
[The myasthenic syndrome after chloroquine].
1999 Jul-Aug
Cadmium-mediated oxidative stress in kidney proximal tubule cells induces degradation of Na+/K(+)-ATPase through proteasomal and endo-/lysosomal proteolytic pathways.
1999 Oct
Assessment of drugs against Cryptosporidium parvum using a simple in vitro screening method.
1999 Sep 15
Chloroquine exerts an additive in vitro anti-HIV type 1 effect when associated with didanosine and hydroxyurea.
1999 Sep 20
Multifocal ERG in chloroquine retinopathy: regional variance of retinal dysfunction.
2000 Jan
[Complete heart block following chronic chloroquine treatment].
2000 May
Coma in a patient with Alzheimer's disease taking low dose trazodone and gingko biloba.
2000 May
Seizures after antimalarial medication in previously healthy persons.
2000 May-Jun
Effect of primaquine standard dose (15 mg/day for 14 days) in the treatment of vivax malaria patients in Thailand.
2001 Dec
The anti-HIV-1 activity of chloroquine.
2001 Feb
Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s.
2001 Jan
The additive in vitro anti-HIV-1 effect of chloroquine, when combined with zidovudine and hydroxyurea.
2001 Jun 15
Cardiac toxicity secondary to long term treatment with chloroquine.
2001 Mar
High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter.
2002 Jun
[Many travellers suffer of side-effects of malaria prophylaxis].
2002 Jun 27
The first molecular evidence that autophagy relates rimmed vacuole formation in chloroquine myopathy.
2002 May
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
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
Acute neuropharmacologic action of chloroquine on cortical neurons in vitro.
2003 Jan 10
[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
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
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
Attenuation of chloroquine-induced renal damage by alpha-lipoic acid: possible antioxidant mechanism.
2004 Sep
Protective effects of different antioxidants and amrinone on vancomycin-induced nephrotoxicity.
2005 Nov
Images in cardiovascular medicine. Contrast-enhanced magnetic resonance imaging of a patient with chloroquine-induced cardiomyopathy confirmed by endomyocardial biopsy.
2006 Aug 22
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
Tetrahydrocurcumin: effect on chloroquine-mediated oxidative damage in rat kidney.
2006 Nov
Autophagy inhibitors chloroquine and LY294002 enhance temozolomide cytotoxicity on cutaneous melanoma cell lines in vitro.
2017 Mar
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:05:06 GMT 2023
Edited
by admin
on Fri Dec 15 15:05:06 GMT 2023
Record UNII
7FY24HE2G3
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY