Amodiaquine

Amodiaquine

Systematic (IUPAC) name
4-[(7-chloroquinolin-4-yl)amino]-2-[(diethylamino)methyl]phenol
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
Molecular mass	355.861 g/mol
SMILES Clc1cc2nccc(c2cc1)Nc3cc(c(O)cc3)CN(CC)CC
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) Y Key:OVCDSSHSILBFBN-UHFFFAOYSA-N Y
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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.

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. The wholesale cost is between 0.05 USD per dose as of 2014.

Medical uses

Amodiaquine has become an important drug in the combination therapy for malaria treatment in Africa.

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. 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. 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.