CDK2; Bcl-2; Bax

Amantadine hydrochloride (0-500 μM, 26 hours) inhibits SARS-CoV-2 replication with IC50 concentrations between 83 and 119 μM [4]. Amantadine hydrochloride (0-100 μg/mL, 24-72 h) significantly inhibits HepG2. Amantadine hydrochloride (0-75 μg/mL, 48 h) blocks the cell cycle in the G0/G1 phase and induces cell swelling [6]. Amantadine hydrochloride (0-75 μg) and swelling of SMMC-7721 cells [6]. /mL, 48 h) can reduce cell cycle-related genes and proteins (cyclin D1, cyclin E and CDK2), reduce Bcl-2 and increase Bax protein and mRNA levels [6]. Cell Viability Assay[4] Cell Line: Vero E6 Cell Concentration: 500 µM, 100 µM, 20 µM, 4 µM and 8 nM Incubation time: 26 hours Results: Concentration of viral nucleic acid in the supernatant after 26 hours of infection at 10°C Reduced dependence (IC50=83 µM) -500 µM. Results in a concentration-dependent reduction of viral nucleic acid in the cytoplasm (IC50=119 µM) 26 hours post-infection. Cell proliferation assay[6] Cell lines: Human HCC cell lines (HepG2 and SMMC-7721) and normal liver cells (L02 cells) Concentrations: 0, 1, 2, 5, 10, 25, 50 and 100 µg/mL Incubation time : 24, 48 and 72 hours Results: Inhibited cell proliferation in a time- and dose-dependent manner in HepG2 and SMMC-7721 cells. Cell cycle analysis[6] Cell lines: HepG2 and SMMC-7721 Cell concentrations: 0, 10, 25, 50 and 75 µg/mL Incubation time: 48 hours Results: Significant increase in the number of HepG2 and SMMC-7721 cells in G0/G1 phase in a dose-dependent manner, and significantly reduced the number of HepG2 cells in the S phase. Apoptosis analysis[6] Cell lines: HepG2 and SMMC-7721 Cell concentrations: 0, 10, 25, 50 and 75 µg/mL Incubation time: 48 hours Results: Significant increase in the percentage of apoptotic HepG2 and SMMC-7721 cells (early- and late-stage apoptosis) in a dose-dependent manner. Western Blot Analysis[6] Cell lines: HepG2 and SMMC-7721 Cell concentrations: 0, 10, 25, 50 and 75 µg/mL Incubation time: 48 h Results: showed downregulation of cyclin D1, cyclin E and CDK2, and showed that HepG2 and Bcl-2 levels were reduced and Bax levels were increased in SMMC-7721 cells. RT-PCR[6] Cell lines: HepG2 and SMMC-7721 Cell concentrations: 0, 10, 25, 50 and 75 µg/mL Incubation time: 48 hours Results: Showed an increase in Bax and a decrease in Bcl-2 gene.

Amantadine hydrochloride (25 mg/kg, IP, once daily for 3 days) inhibits neuromodulation and learning and memory impairments caused by conditioning [5]. Animal model: Fischer 344 rats (4 months old, male, 290-330 g, 15 rats per group) [5] Dosage: 25 mg/kg Administration method: IP, once daily for 3 consecutive days (surgery 15 minutes before the first administration) Results: Inhibition of neuroinflammation and learning and memory impairment caused by surgery, increased GDNF (glial cell line-derived neurotrophic factor) and glial fibrillary acidic protein (star) in the hippocampus morphocyte markers) colocalized.

Cell Line: Vero E6 cells
Concentration: 500 µM, 100 µM, 20 µM, 4 µM, and 8 nM
Incubation Time: 26 h
Result: Caused a concentration-dependent reduction (IC50=83 µM) of viral nucleic acids in the supernatant 26 h after infection at 10-500 µM. Caused a concentration-dependent reduction (IC50=119 µM) of viral nucleic acids in the cytosol 26 h after infection.

Fischer 344 rats (Four-month old, male, 290-330 g, 15 rats each group)
25 mg/kg
Administration: IP, once daily for 3 days (the first dose at 15 min before surgery)

[1]. Emergence of amantadine-resistant influenza A viruses: epidemiological study. J Infect Chemother. 2003;9(3):195-200.

[2]. Amantadine: the journey from fighting flu to treating Parkinson disease. Neurology. 2012;78(14):1096-1099.

[3]. A review of compounds exhibiting anti-orthopoxvirus activity in animal models. Antiviral Res. 2003 Jan;57(1-2):41-52.

[4]. Amantadine Inhibits SARS-CoV-2 In Vitro. Viruses. 2021 Mar 24;13(4):539.

[5]. Amantadine alleviates postoperative cognitive dysfunction possibly by increasing glial cell line-derived neurotrophic factor in rats. Anesthesiology. 2014 Oct;121(4):773-85.

[6]. Amantadine inhibits cellular proliferation and induces the apoptosis of hepatocellular cancer cells in vitro. Int J Mol Med. 2015;36(3):904-910.

Amantadine Hydrochloride can cause developmental toxicity according to state or federal government labeling requirements.
Amantadine Hydrochloride is the hydrochloride salt of amantadine, a synthetic tricyclic amine with antiviral, antiparkinsonian, and antihyperalgesic activities. Amantadine appears to exert its antiviral effect against the influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the release of infectious viral nucleic acids into host cells; furthermore, this agent prevents virus assembly during virus replication. Amantadine exerts its antiparkinsonian effects by stimulating the release of dopamine from striatal dopaminergic nerve terminals and inhibiting its pre-synaptic reuptake. This agent may also exert some anticholinergic effect through inhibition of N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine, resulting in antihyperalgesia.
An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.
See also: Amantadine (has active moiety).

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Drug Indication
Treatment of Parkinson's disease and parkinsonism

C10H18CLN

187.7

187.112

C, 63.99; H, 9.67; Cl, 18.89; N, 7.46

665-66-7

Amantadine; 768-94-5; Amantadine sulfate; 31377-23-8

64150

White to off-white solid powder

1.067g/cm3

225.7ºC at 760 mmHg

>300 °C(lit.)

96ºC

1.558

3.416

2

1

0

12

144

0

Cl[H].N([H])([H])C12C([H])([H])C3([H])C([H])([H])C([H])(C([H])([H])C([H])(C3([H])[H])C1([H])[H])C2([H])[H]

WOLHOYHSEKDWQH-UHFFFAOYSA-N

InChI=1S/C10H17N.ClH/c11-10-4-7-1-8(5-10)3-9(2-7)6-10;/h7-9H,1-6,11H2;1H

adamantan-1-amine;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 6.88 mg/mL (36.65 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)