Amodiaquine dihydrochloride (Amodiaquin dihydrochloride), a member of the 4-aminoquinoline class, is an antimalarial agent that also acts as a potent oral histamine N-methyltransferase inhibitor with a K i value of 18.6 nM. Additionally, it functions as a Nurr1 agonist, targeting the Nurr1-LBD (ligand binding domain) with an EC 50 of approximately 20 μM, demonstrating anti-inflammatory effects [1] [2] [3] [4] [5].

Amodiaquine treatment ranging from 10-20 μM for 4 hours significantly reduces the expression of proinflammatory cytokines (IL-1β, interleukin-6, TNF-α, and iNOS) induced by LPS in a dose-dependent manner. Additionally, at a concentration of 5 μM over 24 hours, Amodiaquine markedly diminishes 6-OHDA-induced cell death in primary dopamine neurons, as evidenced by the preservation of TH+ neuron numbers and dopamine uptake. This neuroprotective effect is corroborated in rat PC12 cells. RT-PCR results from primary microglia treated with 10 μM, 15 μM, and 20 μM Amodiaquine for 4 hours further confirm the suppression of LPS-induced proinflammatory cytokine expression, demonstrating Amodiaquine’s potent anti-inflammatory and neuroprotective activities.

Amodiaquine administration (40 mg/kg; intraperitoneal injection; daily for 3 days) in male ICR mice aged 8-10 weeks with induced intracerebral hemorrhage (ICH) significantly diminished the activation of perihematomal microglia/macrophages and astrocytes. Furthermore, the treatment effectively suppressed ICH-induced mRNA expression levels of IL-1β, CCL2, and CXCL2, concurrently ameliorating the motor dysfunction observed in these animals.