Amodiaquine

Amodiaquine (Amodiaquin), a 4-aminoquinoline class of antimalarial agent, is a potent and orally active histamine N-methyltransferase inhibitor. Amodiaquine is also a Nurr1 agonist and specifically binds to Nurr1-LBD (ligand binding domain) with an EC50 of ~20 μM. Anti-inflammatory effect[1][2][3][4].

Research Areas >> Infection

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

EC50: ~20 μM (Nurr1-LBD (ligand binding domain))[1] Histamine N-methyltransferase[3]

Amodiaquine (10-20 μM; 4 hours) treatment suppresses LPS-induced expression of proinflammatory cytokines (IL-1β, interleukin-6, TNF-α and iNOS) in a dose-dependent manner[1]. Amodiaquine (5 μM; 24 hours) significantly inhibits neurotoxin (6-OHDA-induced cell death in primary dopamine cells as examined by the number of TH+ neurons and dopamine uptake. The neuroprotective effect of Amodiaquine is also observed in rat PC12 cells[1]. RT-PCR[1] Cell Line: Primary microglia Concentration: 10 µM, 15 µM, 20 µM Incubation Time: 4 hours Result: Suppressed LPS-induced expression of proinflammatory cytokines (IL-1β, interleukin-6, TNF-α and iNOS) in a dose-dependent manner.

Amodiaquine (40 mg/kg; intraperitoneal injection; daily; for 3 days; male ICR mice) treatment diminishes perihematomal activation of microglia/macrophages and astrocytes. Amodiaquine also suppresses ICH-induced mRNA expression of IL-1β, CCL2 and CXCL2, and ameliorated motor dysfunction of mice[2]. Animal Model: Male ICR mice (8-10 weeks of age) induced ntracerebral hemorrhage (ICH)[2] Dosage: 40 mg/kg Administration: Intraperitoneal injection; daily; for 3 days Result: Diminished perihematomal activation of microglia/macrophages and astrocytes.

[1]. Chun-Hyung Kim, et al. Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson's disease. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8756-61.

[2]. Keita Kinoshita, et al. A Nurr1 agonist amodiaquine attenuates inflammatory events and neurological deficits in a mouse model of intracerebral hemorrhage. J Neuroimmunol. 2019 May 15;330:48-54.

[3]. Akira Yokoyama, et al. 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.

[4]. M T HOEKENGA. The treatment of acute malaria with single oral doses of amodiaquin, chloroquine, hydroxychloroquine and pyrimethamine. Am J Trop Med Hyg. 1954 Sep;3(5):833-8.

DATA ITEMS CITED :

7

MOLECULAR FORMULA :

C20-H22-Cl-N3-O

MOLECULAR WEIGHT :

355.90

WISWESSER LINE NOTATION :

T66 BNJ EMR DQ C1N2&2& IG

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

72 mg/kg/7W-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - pulmonary emboli Liver - other changes Blood - agranulocytosis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

20 mg/kg/25D-I

TOXIC EFFECTS :

Blood - thrombocytopenia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

29 mg/kg/25D-I

TOXIC EFFECTS :

Blood - thrombocytopenia

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

800 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

550 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

225 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

MUTATION DATA

TYPE OF TEST :

Phage inhibition capacity

TEST SYSTEM :

Bacteria - Escherichia coli

DOSE/DURATION :

5 mg/plate

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 222,311,1989