Amodiaquine 2HCl, a 4-aminoquinoline class of antimalarial agent, is a potent and orally active histamine N-methyltransferase inhibitor with a Ki of 18.6 nM. Amodiaquine 2HCl is also a Nurr1 agonist and specifically binds to Nurr1-LBD (ligand binding domain) with an EC50 of ~20 μM. Anti-inflammatory effect[1]. The subcutaneous injection of amodiaquine (2 and 5 mg/kg) significantly increased the histamine levels in the liver in comparison to saline treated mice. Pretreatment with amodiaquine also improved the survival rate of the hepatitis mice. Amodiaquine partially suppressed increases of tumor necrosis factor (TNF)-alpha in the serum and TNF-alpha mRNA expression in the liver, whereas the expression of interleukin (IL)-18, interferon (IFN)-gamma and IL-12 in the liver was not changed by amodiaquine treatment[2]. Daily administration of a Nurr1 agonist amodiaquine (40 mg/kg, i.p.) from 3 h after ICH (intracerebral hemorrhage) induction diminished perihematomal activation of microglia/macrophages and astrocytes. Amodiaquine also suppressed ICH-induced mRNA expression of IL-1β, CCL2 and CXCL2, and ameliorated motor dysfunction of mice[3].
Amodiaquine 2HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SH-SY5Y cells
10 µM and 15 µM
24 hours
To evaluate the effect of amodiaquine on the expression of insulin-degrading enzyme (IDE), results showed that amodiaquine significantly increased IDE expression
Aging Cell. 2019 Feb;18(1):e12866.
Primary striatal neurons
100 nM
To evaluate the effect of Nurr1 activation on D2 expression. 100 nM AQ increased D2 expression levels in primary striatal neuron cultures of SAL mice.
Transl Psychiatry. 2022 Aug 9;12(1):324.
Primary striatal neurons
10 nM –10μM
24 hours
To assess cell viability and determine the optimal non-cytotoxic concentration. Concentrations >500 nM showed significant cytotoxicity.
Transl Psychiatry. 2022 Aug 9;12(1):324.
Amodiaquine 2HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mastomys natalensis
Litomosoides carinii infection
Oral
5x25mg/kg to 5x100mg/kg
5 consecutive days
Amodiaquine showed marked effectiveness against adult parasites, which were killed and encapsulated in fibrin.
Bull World Health Organ. 1971;44(6):765-70
Mice
Wild-type and knockout mice
Carotid perfusion
0.5 mmol/L
120 seconds
Evaluate the effect of Amodiaquine as an inhibitor of the proton-antiporter on the blood-retinal barrier
Br J Pharmacol. 2015 Oct;172(19):4714-25
Mice
Intracerebral hemorrhage model
Intraperitoneal injection
40 mg/kg/d
Daily
Amodiaquine attenuates inflammatory events and neurological deficits in a mouse model of intracerebral hemorrhage by activating Nurr1
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