Fig. 1 · Structure

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Amantadine hydrochloride

Antiviral Agent

Amantadine (1-Adamantanamine) hydrochloride is an orally avtive and potent antiviral agent with activity against influenza A viruses. Amantadine hydrochloride inhibits several ion channels such as NMDA and M2, and also inhibits Coronavirus ion channels. Amantadine hydrochloride also has anti-orthopoxvirus and anticancer activity. Amantadine hydrochloride can be used for Parkinson's disease, postoperative cognitive dysfunction (POCD) and COVID-19 research.

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In Vitro Studies

In MDCK cells, Amantadine as a single agent had a cytotoxic concentration of 37–40 µg/mL. In Huh7 cells pretreated before SARS-CoV-2 pseudovirus infection, Amantadine inhibited CTSL enzyme activity and blocked infection-induced CTSL activation compared with vehicle. In GFP‐LC3‐transduced HCT116 cells assessed with and without Amantadine, the amantadine-sensitive IAV strain completely failed to relocalise LC3 in its presence. [1,2,3]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Amantadine cytotoxicity in MDCK cells

Cell-based study · MDCK cells [1]

In MDCK cells, Amantadine added as a single agent had a TC50 of 37–40 µg/mL.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
50% cytotoxic concentration (TC50)TC50 37–40 µg/mL[1]

Literature-Reported Treatment Conditions

Treatment concentration
0, 0.001, 0.0032, 0.01, 0.032, 0.1, 0.32, 1, 3.2, 10, 32 and 100 µg/mL
Method
added to MDCK cells in 96-well microplates
Reported limits
Not stated in the sentences used: schedule, vehicle.
Methods and source locations

Compound reported in the paper: Amantadine

The paper names Amantadine without stating the salt or form; not verified as the hydrochloride form supplied as A10060. No dose conversion or lot validation.

Materials and Methods > Cell-Based Assays (S15, S16, S17, S19); Materials and Methods > EC50, TC50, and Synergy Calculations (S28); Results > Cytotoxicity of Antiviral Drugs as Single Agents and in Double and Triple Combinations (S131)

50% cytotoxic concentration (TC50): 50% cytotoxic concentration (TC50); comparator: uninfected cells (cell controls) — Materials and Methods > Cell-Based Assays (S19); Results > Cytotoxicity of Antiviral Drugs as Single Agents and in Double and Triple Combinations (S131)

Amantadine and CTSL activity in Huh7 cells

Cell-based study · Huh7 cells; n = 7 [2]

Huh7 cells were pretreated with 300 μM Amantadine for 1 h before SARS-CoV-2 pseudovirus infection. Compared with vehicle, Amantadine inhibited CTSL enzyme activity and blocked infection-induced CTSL activation.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
CTSL enzyme activity in Huh7 cellsReported result 300 μM amantadine for 1 h: inhibited the enzyme activity and blocked the activation of CTSL induced by SARS-CoV-2 pseudovirus infection.[2]

Literature-Reported Treatment Conditions

Treatment concentration
300 μM
Exposure duration
for 1 h and were then infected with SARS-CoV-2 pseudovirus
Method
pretreated
Co-treatment
Other interventions in this design: SARS-CoV-2 pseudovirus 1.3 × 104 TCID50/ml. Compound effect isolated by the comparison: vehicle.
Reported limits
Not stated in the sentences used: vehicle.
Methods and source locations

Compound reported in the paper: Amantadine

The paper names Amantadine without stating the salt or form; not verified as the hydrochloride form supplied as A10060. No dose conversion or lot validation.

Results > CTSL inhibitors prevent SARS-CoV-2 pseudovirus infection in vitro (S103, S104, S105, S111)

CTSL enzyme activity in Huh7 cells: CTSL enzyme activity in Huh7 cells; comparator: vehicle — Results > CTSL inhibitors prevent SARS-CoV-2 pseudovirus infection in vitro (S103, S104, S111)

Amantadine and LC3 relocalisation in infected HCT116 cells

Cell-based study · GFP‐LC3‐transduced HCT116 cells [3]

Amantadine was added after infection in GFP‐LC3‐transduced HCT116 cells. In the comparison of its presence or absence, the amantadine-sensitive IAV strain completely failed to relocalise LC3 in the presence of Amantadine.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Confocal images of GFP‐LC3‐transduced HCT116 cellsReported result the IAV strain, which is sensitive to amantadine completely fails to relocalise LC3[3]

Literature-Reported Treatment Conditions

Exposure duration
Amantadine was added 3 h postinfection. Samples were fixed at 16 h postinfection
Method
added
Co-treatment
Other interventions in this design: . Compound effect isolated by the comparison: in the presence or absence of amantadine.
Reported limits
Not stated in the sentences used: dose, vehicle.
Methods and source locations

Compound reported in the paper: Amantadine

The paper names Amantadine without stating the salt or form; not verified as the hydrochloride form supplied as A10060. No dose conversion or lot validation.

Results > Influenza A infection activates non‐canonical autophagy via a proton channel (S109, S110); Figure 8 legend (S266, S267, S268)

Confocal images of GFP‐LC3‐transduced HCT116 cells: Confocal images of GFP‐LC3‐transduced HCT116 cells; comparator: absence of amantadine — Results > Influenza A infection activates non‐canonical autophagy via a proton channel (S110); Figure 8 legend (S266)

Specifications

Manufacturer Adooq Bioscience
CAS Number 665-66-7
Applications Antiviral Agent
Formula C10H18ClN
Molecular Weight 187.71
Synonyms 1-Adamantanamine hydrochloride; 1-Adamantylamine hydrochloride; 1-Aminoadamantane hydrochloride
SMILES
NC1(C2)C[C@@H]3C[C@@H](C[C@H]2C3)C1.Cl

Storage & Solubility

In Vitro Solubility

Reported Solubility

No reported solubility data are available for this product.

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Nguyen JT, Hoopes JD, Le MH, et al. Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains in vitro. PLoS One (2010). PMID: 20179772 DOI: 10.1371/journal.pone.0009332 Source material
  2. [2] Zhao MM, Yang WL, Yang FY, et al. Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development. Signal Transduct Target Ther (2021). PMID: 33774649 DOI: 10.1038/s41392-021-00558-8 Source material
  3. [3] Fletcher K, Ulferts R, Jacquin E, et al. The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes. EMBO J (2018). PMID: 29317426 DOI: 10.15252/embj.201797840 Source material

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