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targets (2) enzymes (5)
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Identification
Name Amodiaquine
Accession Number DB00613 (APRD00796)
Type small molecule
Groups approved
Description

A 4-aminoquinoquinoline compound with anti-inflammatory properties. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Amodiaquin
Amodiaquine Hydrochloride
Amodiaquine USP24
Amodiaquine, ring-closed
Salts Not Available
Brand names
Name Company
Basoquin
CAM-AQ1
CAM-AQI
Camochin
Camoquin
Camoquin HCL
Camoquinal
Camoquine
Flavoquin
Flavoquine
Miaquin
First Prev Next Last
Brand mixtures
Brand Name Ingredients
Camoprima Infatabs amodiaquine + primaquine
Categories
  • Antimalarials
  • Amebicides
CAS number 86-42-0
Weight Average: 355.861
Monoisotopic: 355.145140048
Chemical Formula C20H22ClN3O
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Aminoquinolines and Derivatives
  • (Iso)quinolines and Derivatives
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Pyridines and Derivatives
  • Benzene and Derivatives
  • Aryl Halides
  • Aminoquinolines and Derivatives
  • Halobenzenes
  • Aminophenols and Derivatives
  • Aminopyridines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
  • Phenyl Esters
  • Anilines
Pharmacology
Indication For treatment of acute malarial attacks in non-immune subjects.
Pharmacodynamics Amodiaquine, 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 action The 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.
Absorption Rapidly absorbed following oral administration.
Volume of distribution Not Available
Protein binding Not 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.
Route of elimination Not Available
Half life 5.2 ± 1.7 (range 0.4 to 5.5) minutes
Clearance Not Available
Toxicity LD50 (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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 208 dec °C PhysProp
logP 3.7 Not Available
Predicted Properties
Property Value Source
water solubility 8.80e-03 g/l ALOGPS
logP 4.83 ALOGPS
logP 3.76 ChemAxon
logS -4.6 ALOGPS
pKa (strongest acidic) 9.12 ChemAxon
pKa (strongest basic) 10.23 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 48.39 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 103.29 ChemAxon
polarizability 38.89 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D02922 Link_out
KEGG Compound C07626 Link_out
PubChem Compound 2165 Link_out
PubChem Substance 46506940 Link_out
ChemSpider 2080 Link_out
ChEBI 2674 Link_out
ChEMBL 2674 Link_out
Therapeutic Targets Database DAP000699 Link_out
PharmGKB PA448404 Link_out
HET CQA Link_out
Wikipedia http://en.wikipedia.org/wiki/Amodiaquine Link_out
ATC Codes
  • P01BA06
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Ferriprotoporphyrin IX

Pharmacological action: yes
Actions: adduct

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

Pharmacological action: unknown
Actions: inhibitor

Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine

Organism class: human
UniProt ID: P50135 Link_out
Gene: HNMT
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development

UniProt ID: Q16678 Link_out
Gene: CYP1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:19