Function of Amantadine
Amantadine functions primarily as an antiviral agent against influenza A virus and as a treatment for Parkinson's disease and drug-induced extrapyramidal reactions. 1
Antiviral Mechanism and Activity
Amantadine interferes with the replication cycle of influenza A viruses (but not influenza B) by preventing the release of infectious viral nucleic acid into host cells through disruption of the viral M2 protein transmembrane domain. 2, 1 The drug also prevents virus assembly during replication in certain cases. 1
- The specific antiviral activity targets all influenza A virus subtypes (H1N1, H2N2, H3N2) with minimal to no activity against influenza B. 1
- Amantadine binds to the M2 ion channel of influenza A virus, specifically inhibiting viral uncoating and replication. 3
- The drug has been shown to inhibit other viruses in vitro, including SARS-CoV-2, though clinical applications remain under investigation. 2, 4
Clinical Efficacy for Influenza
When used prophylactically, amantadine is approximately 70-90% effective in preventing illness caused by naturally occurring influenza A virus strains. 2
- For treatment, amantadine reduces the duration of fever and systemic symptoms when administered within 48 hours of illness onset, permitting more rapid return to daily activities. 2, 3
- The drug allows subclinical infection to occur while preventing clinical illness, enabling development of protective immune responses for future exposures to antigenically related viruses. 2
- Amantadine does not interfere with the antibody response to influenza vaccine. 2
Neurological Mechanisms
For Parkinson's disease and extrapyramidal reactions, amantadine's mechanism involves both direct and indirect effects on dopamine neurons and functions as a weak, non-competitive NMDA receptor antagonist. 1
- The drug exhibits anticholinergic-like effects clinically (dry mouth, urinary retention, constipation) despite lacking direct anticholinergic activity in animal studies. 1
- Amantadine is less effective than levodopa for Parkinson's disease but produces fewer anticholinergic side effects compared to traditional antiparkinson drugs when treating drug-induced extrapyramidal reactions. 1
Important Clinical Limitations
Widespread resistance has rendered amantadine clinically obsolete for influenza treatment in current practice. 2 Resistance mutations emerge in approximately 30% of treated patients as early as 2-3 days into treatment. 3 The CDC no longer recommends adamantanes for influenza due to high resistance rates among circulating strains. 2
- Side effects occur in 5-33% of recipients, including CNS reactions (nervousness, insomnia, impaired concentration, dizziness) that are more severe in elderly patients. 2, 3, 5
- Dose reductions are required for patients ≥65 years and those with renal insufficiency, as the drug is primarily excreted unchanged in urine. 2, 6
- The elimination half-life extends dramatically in renal impairment (from 11.8 hours in normal function to up to 33.8 days in severe impairment). 6