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Amodiaquine
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Systematic (IUPAC) name |
4-[(7-chloroquinolin-4-yl)amino]-2-[(diethylamino)methyl]phenol
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Clinical data |
AHFS/Drugs.com |
International Drug Names |
Identifiers |
CAS Number |
86-42-0 Y |
ATC code |
P01BA06 (WHO) |
PubChem |
CID 2165 |
DrugBank |
DB00613 Y |
ChemSpider |
2080 Y |
UNII |
220236ED28 Y |
KEGG |
D02922 Y |
ChEBI |
CHEBI:2674 Y |
ChEMBL |
CHEMBL682 Y |
Chemical data |
Formula |
C20H22ClN3O |
Molar mass |
355.861 g/mol |
SMILES
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Clc1cc2nccc(c2cc1)Nc3cc(c(O)cc3)CN(CC)CC
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InChI
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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) Y
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Key:OVCDSSHSILBFBN-UHFFFAOYSA-N Y
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(verify) |
Amodiaquine (trade names Camoquin, Flavoquine), a 4-aminoquinoline compound related to chloroquine, is used as an antimalarial and anti-inflammatory agent.
Amodiaquine has been shown to be more effective than chloroquine in treating chloroquine-resistant Plasmodium falciparum malaria infections and may give more protection than chloroquine when used as weekly prophylaxis. Amodiaquine, like chloroquine, is generally well tolerated. Although licensed, this drug is not marketed in the United States, but is widely available in Africa. Its use, therefore, is probably more practicable in long-term visitors and persons who will reside in Africa.[1]
Amodiaquine is a histamine N-methyltransferase inhibitor.
It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[2] The wholesale cost is between 0.05 USD per dose as of 2014.[3]
Medical uses
Amodiaquine has become an important drug in the combination therapy for malaria treatment in Africa.[4]
Pharmacogenetics
It is bioactivated hepatically to its primary metabolite, N-desethylamodiaquine, by the cytochrome p450 enzyme CYP2C8. Among amodiaquine users, several rare but serious side effects have been reported and linked to variants in the CYP2C8 alleles. CYP2C8*1 is characterized as the wild-type allele, which shows an acceptable safety profile, while CYP2C8*2, *3 and *4 all show a range of "poor metabolizer" phenotypes. People who are poor metabolizers of amodiaquine display lower treatment efficacy against malaria, as well as increased toxicity.[5] Several studies have been conducted to determine the prevalence of CYP2C8 alleles amongst malaria patients in East Africa, and have tentatively shown the variant alleles have significant prevalence in that population.[6] About 3.6% of the population studied showed high risk for a poor reaction to or reduced treatment outcomes when treated with amodiaquine. This information is useful in developing programs of pharmacovigilance in East Africa, and have important clinical considerations for prescribing antimalarial medications in regions with high CYP2C8 variant frequency.
References
- ^ CDC recommendations for travel to areas with malaria
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ "Amodiaquine". International Drug Price Indicator Guide. Retrieved 4 December 2015.
- ^ Kerb, Reinhold; Fux; Morike; Kremsner; Gil; Gleiter; Schwab (2009). "Pharmacogenetics of antimalarial drugs: effect on metabolism and transport". Lancet Infectious Disease 9 (12): 760–774. doi:10.1016/S1473-3099(09)70320-2.
- ^ Elyazar, Iqbal; Hay, Baird (April 2011). "Malaria Distribution, Prevalence, Drug Resistance, and control in Indonesia". Advanced Parasitology. Advances in Parasitology 74 (74): 41–175. doi:10.1016/B978-0-12-385897-9.00002-1. ISBN 9780123858979.
- ^ Roederer, Mary; Mcleod, Juliano (2011). "Can pharmacogenetics improve malaria". Bulletin of World Health Organization 89 (11): 838–845. doi:10.2471/BLT.11.087320.
Antiparasitics – antiprotozoal agents – Chromalveolate antiparasitics (P01)
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Alveo-
late |
Apicom-
plexa |
Conoidasida/
(Coccidiostats) |
Cryptosporidiosis |
- thiazolide (nitazoxanide)
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Isosporiasis |
- trimethoprim/sulfamethoxazole#
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Toxoplasmosis |
- pyrimethamine
- sulfadiazine
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|
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Aconoidasida |
Malaria |
Individual
agents |
Hemozoin
inhibitors |
aminoquinolines |
- (4-): amodiaquine#
- chloroquine#
- Tafenoquine
- (8-): primaquine#
- pamaquine
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|
4-methanolquinolines |
- mefloquine#
- quinine#
- quinidine
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Other |
|
|
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Antifolates |
DHFR inhibitors
(antifols) |
- proguanil#
- chlorproguanil
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Sulfonamides |
- sulfadoxine
- sulfamethoxypyrazine
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Coformulation |
- sulfadoxine/pyrimethamine (SP)#
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|
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Sesquiterpene
lactones |
- artemether#
- artesunate#
- dihydroartemisinin
- artemotil
- artemisinin
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Other |
- atovaquone (with proguanil as Malarone)
- tetracycline
- doxycycline#
- clindamycin
- pyronaridine
- piperaquine
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|
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Combi-
nations |
Fixed-dose (coformulated) ACTs |
- artemether/lumefantrine#
- artesunate/amodiaquine (ASAQ)
- artesunate/mefloquine (ASMQ)
- dihydroartemisinin/piperaquine
- artesunate/pyronaridine
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Other combinations
(not co-formulated) |
- artesunate/SP
- artesunate/mefloquine
- quinine/tetracycline
- quinine/doxycycline
- quinine/clindamycin
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Babesiosis |
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Cilio-
phora |
- Balantidiasis: Tetracycline
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|
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Hetero-
kont |
- Blastocystosis: Metronidazole
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Histaminergics
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Receptor
(ligands) |
H1 |
- Agonists: 2-Pyridylethylamine
- Betahistine
- Histamine
- HTMT
- UR-AK49
- Antagonists: First-generation: 4-Methyldiphenhydramine
- Alimemazine
- Antazoline
- Azatadine
- Bamipine
- Benzatropine (benztropine)
- Bepotastine
- Bromazine
- Brompheniramine
- Buclizine
- Captodiame
- Carbinoxamine
- Chlorcyclizine
- Chloropyramine
- Chlorothen
- Chlorphenamine
- Chlorphenoxamine
- Cinnarizine
- Clemastine
- Clobenzepam
- Clocinizine
- Cloperastine
- Cyclizine
- Cyproheptadine
- Dacemazine
- Decloxizine
- Deptropine
- Dexbrompheniramine
- Dexchlorpheniramine
- Dimenhydrinate
- Dimetindene
- Diphenhydramine
- Diphenylpyraline
- Doxylamine
- Embramine
- Etodroxizine
- Etybenzatropine (ethylbenztropine)
- Etymemazine
- Fenethazine
- Flunarizine
- Histapyrrodine
- Homochlorcyclizine
- Hydroxyethylpromethazine
- Hydroxyzine
- Isopromethazine
- Isothipendyl
- Meclozine
- Medrylamine
- Mepyramine (pyrilamine)
- Mequitazine
- Methafurylene
- Methapyrilene
- Methdilazine
- Moxastine
- Orphenadrine
- Oxatomide
- Oxomemazine
- Phenindamine
- Pheniramine
- Phenyltoloxamine
- Pimethixene
- Piperoxan
- Pipoxizine
- Promethazine
- Propiomazine
- Pyrrobutamine
- Talastine
- Thenalidine
- Thenyldiamine
- Thiazinamium
- Thonzylamine
- Tolpropamine
- Tripelennamine
- Triprolidine
- Second/third-generation: Acrivastine
- Alinastine
- Astemizole
- Azelastine
- Bamirastine
- Barmastine
- Bepiastine
- Bepotastine
- Bilastine
- Cabastinen
- Carebastine
- Cetirizine
- Clemastine
- Clemizole
- Clobenztropine
- Desloratadine
- Dorastine
- Ebastine
- Efletirizine
- Emedastine
- Epinastine
- Fexofenadine
- Flezelastine
- Ketotifen
- Latrepirdine
- Levocabastine
- Levocetirizine
- Linetastine
- Loratadine
- Mapinastine
- Mebhydrolin
- Mizolastine
- Moxastine
- Noberastine
- Octastine
- Olopatadine
- Perastine
- Pibaxizine
- Piclopastine
- Quifenadine
- Rocastine
- Rupatadine
- Setastine
- Talastine
- Temelastine
- Terfenadine
- Vapitadine
- Zepastine
- Non-generational: Atypical antipsychotics (e.g., aripiprazole, asenapine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, zotepine)
- Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline)
- Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine)
- Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene)
- Unknown/unsorted: Belarizine
- Elbanizine
- Flotrenizine
- Napactadine
- Tagorizine
- Trelnarizine
- Trenizine
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H2 |
- Agonists: Amthamine
- Betazole
- Dimaprit
- Histamine
- HTMT
- Impromidine
- UR-AK49
- Antagonists: Bisfentidine
- Burimamide
- Cimetidine
- Dalcotidine
- Donetidine
- Ebrotidine
- Etintidine
- Famotidine
- Isolamtidine
- Lafutidine
- Lamtidine
- Lavoltidine (loxtidine)
- Lupitidine
- Metiamide
- Mifentidine
- Niperotidine
- Nizatidine
- Osutidine
- Oxmetidine
- Pibutidine
- Quisultazine (quisultidine)
- Ramixotidine
- Ranitidine
- Roxatidine
- Sufotidine
- Tiotidine
- Tuvatidine
- Venritidine
- Xaltidine
- Zolantidine
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H3 |
- Agonists: α-Methylhistamine
- Cipralisant
- Histamine
- Imetit
- Immepip
- Immethridine
- Methimepip
- Proxyfan
- Antagonists: A-349,821
- A-423,579
- ABT-239
- ABT-652
- AZD5213
- Betahistine
- Burimamide
- Ciproxifan
- Clobenpropit
- Conessine
- Enerisant
- GSK-189,254
- Impentamine
- Iodophenpropit
- Irdabisant
- JNJ-5207852
- MK-0249
- NNC 38-1049
- PF-03654746
- Pitolisant
- SCH-79687
- Thioperamide
- VUF-5681
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H4 |
- Agonists: 4-Methylhistamine
- α-Methylhistamine
- Histamine
- OUP-16
- VUF-8430
- Antagonists: JNJ-7777120
- Mianserin
- Thioperamide
- Toreforant
- VUF-6002
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|
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Transporter
(inhibitors) |
VMATs |
TAAR1 inactive |
- Amiodarone
- APP
- AZIK
- Bietaserpine
- Deserpidine
- Dihydrotetrabenazine
- Efavirenz
- GBR-12935
- GZ-793A
- Ibogaine
- Ketanserin
- Lobeline
- Methoxytetrabenazine
- NBI-98854
- Reserpine
- Rose bengal
- SD-809
- Tetrabenazine
- Vanoxerine (GBR-12909)
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TAAR1 active |
- Amphetamine
- Methamphetamine
- MDMA
- Phenethylamine
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Enzyme
(inhibitors) |
HDC |
- Catechin
- Meciadanol
- Naringenin
- Tritoqualine
|
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HNMT |
- Amodiaquine
- Diphenhydramine
- Harmaline
- Metoprine
- Quinacrine
- SKF-91,488
- Tacrine
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DAO |
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Others |
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UpToDate Contents
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English Journal
- Application of an LC-MS/MS method for reliable determination of amodiaquine, N-desethylamodiaquine, artesunate and dihydroartemisinin in human plasma for a bioequivalence study in healthy Indian subjects.
- Rathod DM1, Patel KR2, Mistri HN2, Jangid AG2, Shrivastav PS3, Sanyal M4.
- Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2016 May 30;124:67-78. doi: 10.1016/j.jpba.2016.02.021. Epub 2016 Feb 22.
- A sensitive and high throughput bioanalytical method has been developed for reliable determination of amodiaquine (AQ), N-desethylamodiaquine (DEAQ), artesunate (AS) and dihydroartemisinin (DHA) in human plasma by LC-MS/MS. The method employs a solid phase extraction procedure without an evaporation
- PMID 26930583
- Lopinavir/ritonavir enhanced the antimalarial activity of amodiaquine and artesunate in a mouse model of Plasmodium berghei.
- Abiodun OO1, Gbimadee N1, Gbotosho GO1.
- Journal of chemotherapy (Florence, Italy).J Chemother.2016 May 5:1-5. [Epub ahead of print]
- Treatment of malaria and HIV in co-infected patients remains a challenge due to the limited information on interaction between drugs used for the treatment of the two infections. Thus, this study evaluated the interaction between lopinavir/ritonavir (LR) and artesunate (AS), amodiaquine (AQ) or a fi
- PMID 26900802
- Degradation of Artemisinin-Based Combination Therapies Under Tropical Conditions.
- Hall Z1, Allan EL1, van Schalkwyk DA1, van Wyk A1, Kaur H2.
- The American journal of tropical medicine and hygiene.Am J Trop Med Hyg.2016 May 4;94(5):993-1001. doi: 10.4269/ajtmh.15-0665. Epub 2016 Mar 7.
- Poor quality antimalarials, including falsified, substandard, and degraded drugs, are a serious health concern in malaria-endemic countries. Guidelines are lacking on how to distinguish between substandard and degraded drugs. "Forced degradation" in an oven was carried out on three common artemisini
- PMID 26951346
Japanese Journal
- Comparison of the in vitro Effects of One-day Exposure to Amodiaquine and Praziquantel on Schistosoma mansoni Adult Worm Pairs
- In vitro effects of amodiaquine on paired Schistosoma mansoni adult worms at concentrations of less than 5 μg/mL
- The Tyrosine Kinase Inhibitor Nilotinib Selectively Inhibits CYP2C8 Activities in Human Liver Microsomes
Related Links
- Amodiaquine has been shown to be more effective than chloroquine in treating chloroquine-resistant Plasmodium falciparum malaria infections and may afford more protection than chloroquine when used as weekly prophylaxis. Amodiaquine ...
- Amodiaquine generic is an antimalarial agent, prescribed for malaria either alone or with other medications.
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