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Identification
NameAmodiaquine
Accession NumberDB00613  (APRD00796)
Typesmall molecule
Groupsapproved
Description

A 4-aminoquinoquinoline compound with anti-inflammatory properties. [PubChem]

Structure
Thumb
SynonymsNot Available
Salts
Name/CAS Structure Properties
Amodiaquine Hydrochloride
Thumb
  • InChI Key: ROEBJVHPINPMKL-UHFFFAOYSA-N
  • Monoisotopic Mass: 427.098495526
  • Average Mass: 428.783
DBSALT000647
Brand names
NameCompany
BasoquinNot Available
CamoquinParke Davis
FlavoquineNot Available
Brand mixtures
Brand NameIngredients
Camoprima Infatabsamodiaquine + primaquine
CategoriesNot Available
CAS number86-42-0
WeightAverage: 355.861
Monoisotopic: 355.145140048
Chemical FormulaC20H22ClN3O
InChI KeyInChIKey=OVCDSSHSILBFBN-UHFFFAOYSA-N
InChI
InChI=1S/C20H22ClN3O/c1-3-24(4-2)13-14-11-16(6-8-20(14)25)23-18-9-10-22-19-12-15(21)5-7-17(18)19/h5-12,25H,3-4,13H2,1-2H3,(H,22,23)
IUPAC Name
4-[(7-chloroquinolin-4-yl)amino]-2-[(diethylamino)methyl]phenol
SMILES
CCN(CC)CC1=C(O)C=CC(NC2=C3C=CC(Cl)=CC3=NC=C2)=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassAminoquinolines and Derivatives
Direct parentAminoquinolines and Derivatives
Alternative parentsAminophenols; Aminopyridines and Derivatives; Chlorobenzenes; Aryl Chlorides; Tertiary Amines; Enols; Secondary Amines; Polyamines; Organochlorides
Substituentsaminophenol; phenol derivative; chlorobenzene; aminopyridine; pyridine; benzene; aryl chloride; aryl halide; tertiary amine; polyamine; enol; secondary amine; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminoquinolines and derivatives. These are organic compounds containing an amino group attached to a quinoline ring system.
Pharmacology
IndicationFor treatment of acute malarial attacks in non-immune subjects.
PharmacodynamicsAmodiaquine, a 4-aminoquinoline similar to chloroquine in structure and activity, has been used as both an antimalarial and an anti-inflammatory agent for more than 40 years. Amodiaquine is at least as effective as chloroquine, and is effective against some chloroquine-resistant strains, although resistance to amodiaquine has been reported. The mode of action of amodiaquine has not yet been determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac conductivity, and produce vasodilatation with resultant hypotension. They depress respiration and cause diplopia, dizziness and nausea.
Mechanism of actionThe mechanism of plasmodicidal action of amodiaquine 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. The drug binds the free heme preventing the parasite from converting it to a form less toxic. This drug-heme complex is toxic and disrupts membrane function.
AbsorptionRapidly absorbed following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic biotransformation to desethylamodiaquine (the principal biologically active metabolite) is the predominant route of amodiaquine clearance with such a considerable first pass effect that very little orally administered amodiaquine escapes untransformed into the systemic circulation.

SubstrateEnzymesProduct
Amodiaquine
desethylamodiaquineDetails
Route of eliminationNot Available
Half life5.2 ± 1.7 (range 0.4 to 5.5) minutes
ClearanceNot Available
ToxicityLD50 (mouse, intraperitoneal) 225 mg/kg, LD50 (mouse, oral) 550 mg/kg. Symptoms of overdose include headache, drowsiness, visual disturbances, vomiting, hypokalaemia, cardiovascular collapse and cardiac and respiratory arrest. Hypotension, if not treated, may progress rapidly to shock. Electrocardiograms (ECG) may reveal atrial standstill, nodal rhythm, prolonged intraventricular conduction time, broadening of the QRS complex, and progressive bradycardia leading to ventricular fibrillation and/or arrest.
Affected organisms
  • Plasmodium
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9818
Blood Brain Barrier + 0.7306
Caco-2 permeable + 0.5966
P-glycoprotein substrate Substrate 0.7168
P-glycoprotein inhibitor I Non-inhibitor 0.8782
P-glycoprotein inhibitor II Inhibitor 0.8387
Renal organic cation transporter Non-inhibitor 0.5943
CYP450 2C9 substrate Non-substrate 0.7898
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Non-substrate 0.5136
CYP450 1A2 substrate Inhibitor 0.8347
CYP450 2C9 substrate Non-inhibitor 0.5836
CYP450 2D6 substrate Inhibitor 0.7582
CYP450 2C19 substrate Inhibitor 0.5416
CYP450 3A4 substrate Non-inhibitor 0.7203
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9202
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.8452
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.4801 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7619
hERG inhibition (predictor II) Inhibitor 0.7306
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point206-208Burckhalter, J.H., Jones, E.M., Rawlins, A.L., Tendick, F.H, and 2,474,821; July 5,1949; assigned to Parke, Davis & Co.
logP3.7Not Available
Predicted Properties
PropertyValueSource
water solubility8.80e-03 g/lALOGPS
logP4.83ALOGPS
logP3.76ChemAxon
logS-4.6ALOGPS
pKa (strongest acidic)9.12ChemAxon
pKa (strongest basic)10.23ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area48.39ChemAxon
rotatable bond count6ChemAxon
refractivity103.29ChemAxon
polarizability38.89ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Burckhalter, J.H., Jones, E.M., Rawlins, A.L., Tendick, F.H, and 2,474,821; July 5,1949; assigned to Parke, Davis & Co.

General Reference
  1. Jewell H, Maggs JL, Harrison AC, O’Neill PM, Ruscoe JE, Park BK: Role of hepatic metabolism in the bioactivation and detoxication of amodiaquine. Xenobiotica. 1995 Feb;25(2):199-217. Pubmed
  2. Harrison AC, Kitteringham NR, Clarke JB, Park BK: The mechanism of bioactivation and antigen formation of amodiaquine in the rat. Biochem Pharmacol. 1992 Apr 1;43(7):1421-30. Pubmed
External Links
ResourceLink
KEGG DrugD02922
KEGG CompoundC07626
PubChem Compound2165
PubChem Substance46506940
ChemSpider2080
ChEBI2674
ChEMBLCHEMBL682
Therapeutic Targets DatabaseDAP000699
PharmGKBPA448404
HETCQA
WikipediaAmodiaquine
ATC CodesP01BA06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Fe(II)-protoporphyrin IX

Kind: small molecule

Organism: Plasmodium falciparum

Pharmacological action: yes

Actions: adduct

Components

Name UniProt ID Details

References:

  1. de Villiers KA, Marques HM, Egan TJ: The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials. J Inorg Biochem. 2008 Aug;102(8):1660-7. Epub 2008 Apr 20. Pubmed
  2. Weissbuch I, Leiserowitz L: Interplay between malaria, crystalline hemozoin formation, and antimalarial drug action and design. Chem Rev. 2008 Nov;108(11):4899-914. Pubmed
  3. Sullivan DJ Jr, Gluzman IY, Russell DG, Goldberg DE: On the molecular mechanism of chloroquine’s antimalarial action. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11865-70. Pubmed
  4. Schwedhelm KF, Horstmann M, Faber JH, Reichert Y, Bringmann G, Faber C: The novel antimalarial compound dioncophylline C forms a complex with heme in solution. ChemMedChem. 2007 Apr;2(4):541-8. Pubmed
  5. Egan TJ, Ncokazi KK: Effects of solvent composition and ionic strength on the interaction of quinoline antimalarials with ferriprotoporphyrin IX. J Inorg Biochem. 2004 Jan;98(1):144-52. Pubmed

2. Histamine N-methyltransferase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Histamine N-methyltransferase P50135 Details

References:

  1. Yokoyama A, Mori S, Takahashi HK, Kanke T, Wake H, Nishibori M: Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice. Eur J Pharmacol. 2007 Mar 8;558(1-3):179-84. Epub 2006 Nov 22. Pubmed
  2. Nowak JZ, Zandarowska E: Effect of amodiaquine on histamine level and histamine-methyltransferase activity in the rat brain. Arch Immunol Ther Exp (Warsz). 1980;28(6):927-30. Pubmed
  3. Barth H, Lorenz W, Troidl H: Effect of amodiaquine on gastric histamine methyltransferase and on histamine-stimulated gastric secretion. Br J Pharmacol. 1975 Nov;55(3):321-7. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

1. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Li XQ, Bjorkman A, Andersson TB, Ridderstrom M, Masimirembwa CM: Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J Pharmacol Exp Ther. 2002 Feb;300(2):399-407. Pubmed
  4. Walsky RL, Obach RS: Validated assays for human cytochrome P450 activities. Drug Metab Dispos. 2004 Jun;32(6):647-60. Pubmed

2. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1B1 Q16678 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on March 28, 2014 09:30