Nootropic profile
Amantadine
An NMDA receptor antagonist and weak dopamine agonist originally developed as an antiviral, now used for Parkinson's disease and off-label for cognitive fatigue and TBI recovery.
Best for
Educational only: this is not medical advice. Always check with a qualified healthcare professional before starting any supplement.
What is Amantadine?
Amantadine (marketed as Symmetrel, Gocovri, and Osmolex) is a unique pharmacological agent with a dual mechanism of action as both an NMDA glutamate receptor antagonist and a dopamine-enhancing agent.
What it does for you
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How to take it
- Parkinson's disease: 100 mg twice daily, with some patients requiring up to 400 mg daily; extended-release formulations (Gocovri) are dosed at 137-274 mg...
- Traumatic brain injury: 100-200 mg twice daily (200-400 mg total daily dose), as used in the Giacino et al. (2012) NEJM trial demonstrating accelerated recovery
- Cognitive fatigue: 100-200 mg daily, typically taken in the morning or split into morning and midday doses to avoid insomnia
- Starting dose: 100 mg once daily for the first week, increasing to 100 mg twice daily based on tolerability; renal dose adjustment required for patients...
- Timing: Morning and early afternoon dosing preferred to minimise insomnia; last dose should generally be taken no later than 4 PM
Watch out for
- Common side effects: Insomnia, dizziness, nausea, dry mouth, constipation, and orthostatic hypotension are the most frequently reported adverse effects,...
- Livedo reticularis: A distinctive mottled, purplish discolouration of the skin (particularly on the legs) occurs in approximately 5-10% of patients and is...
- CNS effects: Can cause hallucinations, confusion, agitation, and in rare cases psychotic episodes, particularly in elderly patients or those with...
- Renal clearance: Amantadine is primarily excreted unchanged by the kidneys; dose reduction is essential in patients with renal impairment to prevent...
- Discontinuation: Abrupt withdrawal should be avoided as it can precipitate neuroleptic malignant syndrome-like reactions, Parkinsonian crisis, or rebound...
The science, if you're curious.
- Acts as an uncompetitive antagonist at NMDA-type glutamate receptors, blocking excessive calcium influx through the receptor channel and providing...
- Increases dopamine release from presynaptic terminals in the striatum and prefrontal cortex, improving dopaminergic signalling involved in motivation,...
- Blocks the dopamine transporter (DAT) to a modest degree, prolonging dopamine's action at post-synaptic receptors in mesolimbic and mesocortical pathways
- Interacts with sigma-1 receptors, which are involved in neuroplasticity, calcium signalling, and neuroprotection, potentially contributing to its cognitive...
Where to find it
- Giacino et al. (2012): "Placebo-controlled trial of amantadine for severe traumatic brain injury" in the New England Journal of Medicine, the landmark trial demonstrating accelerated functional recovery
- Crosby et al. (2012): "Amantadine for traumatic brain injury" in the Annals of Pharmacotherapy, reviewing the evidence for cognitive and functional benefits
- Hubsher et al. (2012): "Amantadine: the journey from fighting flu to treating Parkinson disease" in Neurology, reviewing the drug's pharmacological history and mechanisms
- FDA prescribing information: Complete prescribing information for Symmetrel (amantadine hydrochloride) including pharmacokinetics, clinical data, and comprehensive safety warnings
- Sawyer et al. (2008): "Use of amantadine for cognitive impairment" review in the American Journal of Physical Medicine and Rehabilitation covering off-label cognitive applications
Frequently asked
An NMDA receptor antagonist and weak dopamine agonist originally developed as an antiviral, now used for Parkinson's disease and off-label for cognitive fatigue and TBI recovery.
The main benefits people report from Amantadine are: Cognitive Enhancement, Energy, Focus, Longevity, Memory, Mood, Motivation.
Parkinson's disease: 100 mg twice daily, with some patients requiring up to 400 mg daily; extended-release formulations (Gocovri) are dosed at 137-274 mg...Traumatic brain injury: 100-200 mg twice daily (200-400 mg total daily dose), as used in the Giacino et al. (2012) NEJM trial demonstrating...
Common side effects: Insomnia, dizziness, nausea, dry mouth, constipation, and orthostatic hypotension are the most frequently reported adverse effects,...Livedo reticularis: A distinctive mottled, purplish discolouration of the skin (particularly on the legs) occurs in approximately 5-10% of patien...
Acts as an uncompetitive antagonist at NMDA-type glutamate receptors, blocking excessive calcium influx through the receptor channel and providing...Increases dopamine release from presynaptic terminals in the striatum and prefrontal cortex, improving dopaminergic signalling involved in motivation,....
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