Amodiaquine
Identification
- Summary
Amodiaquine is an antimalarial drug.
- Generic Name
- Amodiaquine
- DrugBank Accession Number
- DB00613
- Background
A 4-aminoquinoquinoline compound with anti-inflammatory properties.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 355.861
Monoisotopic: 355.145140048 - Chemical Formula
- C20H22ClN3O
- Synonyms
- Amodiaquina
- Amodiaquine
- Amodiaquinum
- External IDs
- NSC-13453
- S. N. 10751
- SN 10,751
Pharmacology
- Indication
For treatment of acute malarial attacks in non-immune subjects.
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- 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.
Target Actions Organism AFe(II)-protoporphyrin IX binderPlasmodium falciparum UHistamine N-methyltransferase inhibitorHumans - 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.
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- Route of elimination
Not Available
- Half-life
5.2 ± 1.7 (range 0.4 to 5.5) minutes
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The metabolism of Amodiaquine can be increased when combined with Abatacept. Abiraterone The metabolism of Amodiaquine can be decreased when combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Amodiaquine. Acebutolol The risk or severity of QTc prolongation can be decreased when Amodiaquine is combined with Acebutolol. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Amodiaquine. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Amodiaquine dihydrochloride dihydrate K6PW2S574L 6398-98-7 YVNAYSHNIILOJS-UHFFFAOYSA-N Amodiaquine hydrochloride HOE64181MP 69-44-3 ROEBJVHPINPMKL-UHFFFAOYSA-N - International/Other Brands
- Basoquin / Camoquin (Parke Davis) / Flavoquine
Categories
- ATC Codes
- P01BF03 — Artesunate and amodiaquine
- P01BF — Artemisinin and derivatives, combinations
- P01B — ANTIMALARIALS
- P01 — ANTIPROTOZOALS
- P — ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
- Drug Categories
- Aminoquinolines
- Anti-Infective Agents
- Antimalarials
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Antiprotozoals
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- P-glycoprotein inhibitors
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Quinolines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 4-aminoquinolines. These are organic compounds containing an amino group attached to the 4-position of a quinoline ring system.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Aminoquinolines and derivatives
- Direct Parent
- 4-aminoquinolines
- Alternative Parents
- Chloroquinolines / p-Aminophenols / Phenylmethylamines / Aniline and substituted anilines / Benzylamines / 1-hydroxy-2-unsubstituted benzenoids / Aminopyridines and derivatives / Aralkylamines / Aryl chlorides / Heteroaromatic compounds show 7 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 4-aminoquinoline / Amine / Aminophenol / Aminopyridine / Aniline or substituted anilines / Aralkylamine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- quinolines, phenols (CHEBI:2674) / a small molecule (CPD-10889)
- Affected organisms
- Plasmodium
Chemical Identifiers
- UNII
- 220236ED28
- CAS number
- 86-42-0
- InChI Key
- 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
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 References
- 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. [Article]
- 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. [Article]
- External Links
- Human Metabolome Database
- HMDB0014751
- KEGG Drug
- D02922
- KEGG Compound
- C07626
- PubChem Compound
- 2165
- PubChem Substance
- 46506940
- ChemSpider
- 2080
- BindingDB
- 50041457
- 720
- ChEBI
- 2674
- ChEMBL
- CHEMBL682
- ZINC
- ZINC000000608172
- Therapeutic Targets Database
- DAP000699
- PharmGKB
- PA448404
- PDBe Ligand
- CQA
- Wikipedia
- Amodiaquine
- PDB Entries
- 2aou / 4fgz / 4mwz
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Pharmacoeconomics
- Manufacturers
- Parke davis div warner lambert co
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet, film coated 150 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 206-208 Burckhalter, J.H., Jones, E.M., Rawlins, A.L., Tendick, F.H, and 2,474,821; July 5,1949; assigned to Parke, Davis & Co. logP 3.7 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0088 mg/mL ALOGPS logP 4.83 ALOGPS logP 3.8 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 9.1 Chemaxon pKa (Strongest Basic) 10.17 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 48.39 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 103.29 m3·mol-1 Chemaxon Polarizability 38.89 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - 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 inhibitor Non-inhibitor 0.5836 CYP450 2D6 inhibitor Inhibitor 0.7582 CYP450 2C19 inhibitor Inhibitor 0.5416 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 198.8517239 predictedDarkChem Lite v0.1.0 [M-H]- 189.11505 predictedDeepCCS 1.0 (2019) [M+H]+ 199.6617239 predictedDarkChem Lite v0.1.0 [M+H]+ 191.54535 predictedDeepCCS 1.0 (2019) [M+Na]+ 198.6832239 predictedDarkChem Lite v0.1.0 [M+Na]+ 199.90904 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
References
- 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. doi: 10.1016/j.jinorgbio.2008.04.001. Epub 2008 Apr 20. [Article]
- Weissbuch I, Leiserowitz L: Interplay between malaria, crystalline hemozoin formation, and antimalarial drug action and design. Chem Rev. 2008 Nov;108(11):4899-914. doi: 10.1021/cr078274t. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Histamine n-methyltransferase activity
- Specific Function
- Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
- Gene Name
- HNMT
- Uniprot ID
- P50135
- Uniprot Name
- Histamine N-methyltransferase
- Molecular Weight
- 33294.765 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- 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 un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- 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. doi: 10.1124/jpet.300.2.399. [Article]
- Ma B, Subramanian R, Schrag ML, Rodrigues AD, Tang C: Cytochrome P450 2C8 (CYP2C8)-mediated hydroxylation of an endothelin ETA receptor antagonist in human liver microsomes. Drug Metab Dispos. 2004 May;32(5):473-8. doi: 10.1124/dmd.32.5.473. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d 24-hydroxylase activity
- Specific Function
- 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 un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- 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. doi: 10.1124/jpet.300.2.399. [Article]
- Johansson T, Jurva U, Gronberg G, Weidolf L, Masimirembwa C: Novel metabolites of amodiaquine formed by CYP1A1 and CYP1B1: structure elucidation using electrochemistry, mass spectrometry, and NMR. Drug Metab Dispos. 2009 Mar;37(3):571-9. doi: 10.1124/dmd.108.025171. Epub 2008 Dec 15. [Article]
- Scarsi KK, Fehintola FA, Ma Q, Aweeka FT, Darin KM, Morse GD, Akinola IT, Adedeji WA, Lindegardh N, Tarning J, Ojengbede O, Adewole IF, Taiwo B, Murphy RL, Akinyinka OO, Parikh S: Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy. J Antimicrob Chemother. 2014 May;69(5):1370-6. doi: 10.1093/jac/dkt513. Epub 2014 Jan 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- 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 un...
- Gene Name
- CYP1B1
- Uniprot ID
- Q16678
- Uniprot Name
- Cytochrome P450 1B1
- Molecular Weight
- 60845.33 Da
References
- 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. doi: 10.1124/jpet.300.2.399. [Article]
- Johansson T, Jurva U, Gronberg G, Weidolf L, Masimirembwa C: Novel metabolites of amodiaquine formed by CYP1A1 and CYP1B1: structure elucidation using electrochemistry, mass spectrometry, and NMR. Drug Metab Dispos. 2009 Mar;37(3):571-9. doi: 10.1124/dmd.108.025171. Epub 2008 Dec 15. [Article]
- Scarsi KK, Fehintola FA, Ma Q, Aweeka FT, Darin KM, Morse GD, Akinola IT, Adedeji WA, Lindegardh N, Tarning J, Ojengbede O, Adewole IF, Taiwo B, Murphy RL, Akinyinka OO, Parikh S: Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy. J Antimicrob Chemother. 2014 May;69(5):1370-6. doi: 10.1093/jac/dkt513. Epub 2014 Jan 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- 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...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Wennerholm A, Nordmark A, Pihlsgard M, Mahindi M, Bertilsson L, Gustafsson LL: Amodiaquine, its desethylated metabolite, or both, inhibit the metabolism of debrisoquine (CYP2D6) and losartan (CYP2C9) in vivo. Eur J Clin Pharmacol. 2006 Jul;62(7):539-46. doi: 10.1007/s00228-006-0121-3. Epub 2006 Jun 17. [Article]
- Bapiro TE, Egnell AC, Hasler JA, Masimirembwa CM: Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data based on 1 in vivo study.
- General Function
- Steroid hydroxylase activity
- Specific Function
- 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 un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Wennerholm A, Nordmark A, Pihlsgard M, Mahindi M, Bertilsson L, Gustafsson LL: Amodiaquine, its desethylated metabolite, or both, inhibit the metabolism of debrisoquine (CYP2D6) and losartan (CYP2C9) in vivo. Eur J Clin Pharmacol. 2006 Jul;62(7):539-46. doi: 10.1007/s00228-006-0121-3. Epub 2006 Jun 17. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Senarathna SM, Page-Sharp M, Crowe A: The Interactions of P-Glycoprotein with Antimalarial Drugs, Including Substrate Affinity, Inhibition and Regulation. PLoS One. 2016 Apr 5;11(4):e0152677. doi: 10.1371/journal.pone.0152677. eCollection 2016. [Article]
- A Chemical Approach Towards Understanding the Mechanism and Reversal of Drug Resistance in Plasmodium falciparum: Is it Viable? [File]
Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:53