Pharmacology · Dopaminergic antiparkinson agents (levodopa and amantadine)

Amantadine !

An old antiviral that helps Parkinson disease, mainly levodopa-induced dyskinesia. It is cleared by the kidney and can cause livedo reticularis.

Updated 2026-11-01

Class: Dopaminergic antiparkinson agents (levodopa and amantadine)
Ion channel: NMDA glutamate receptor (channel pore)
ATC code: N04BB01

NMDA glutamate receptor (channel pore)Amantadine

The figure shows memantine, a related adamantane drug, in the pore of the rat NMDA receptor; amantadine is a weaker NMDA receptor antagonist.

Target in 3D: NMDA glutamate receptor (channel pore). PDB structure 7SAD (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Amantadine is a weak, noncompetitive NMDA receptor antagonist and appears to increase dopamine release in the striatum. Blocking glutamate signalling in the basal ganglia reduces levodopa-induced dyskinesia. It also has anticholinergic-like effects. As an antiviral it blocked the M2 ion channel of influenza A, but circulating strains are now resistant.

Amantadine blocks NMDA glutamate receptors
Striatal dopamine release increases
Overactive basal ganglia circuits calm down
Dyskinesia and rigidity lessen

Pharmacokinetics

Absorption: Well absorbed by mouth
Elimination: Mainly unchanged in the urine; accumulates in kidney failure
Half-life: About 17 hours in healthy adults (wide range), longer in older people and in kidney disease

Indications

Parkinson disease, and dyskinesia caused by levodopa Parkinson disease →
Drug-induced extrapyramidal reactions Antipsychotic-induced movement disorders (dystonia, akathisia, parkinsonism, tardive dyskinesia) →
Influenza A (labelled), but no longer recommended because of widespread resistance Influenza (flu) →

Adverse effects

Common

Dizziness, insomnia, nausea
Livedo reticularis (mottled skin, usually on the legs)
Ankle and leg oedema
Dry mouth, constipation, urinary retention
Orthostatic hypotension

Contraindications

Hypersensitivity to amantadine
Untreated angle-closure glaucoma (avoided); caution in kidney failure, heart failure, epilepsy and psychosis

Key interactions

Anticholinergic drugs: More atropine-like effects and confusion
Memantine and other NMDA antagonists: Additive NMDA blockade; caution
Live attenuated (intranasal) influenza vaccine: Possible interference with the vaccine virus
Alcohol and sedatives: More dizziness, confusion and hypotension

What is monitored

Kidney function (creatinine clearance)
Mental state, mood and suicidal thoughts
Oedema, weight and signs of heart failure
Skin of the legs (livedo reticularis)

Administration and safety

Not stopped abruptly in Parkinson disease; tapered
Immediate-release and extended-release forms are different products
Extended-release capsules are usually given at bedtime; other forms at the same times each day

Nursing care

Check kidney function, especially in older adults
Watch for confusion, hallucinations and low mood
Look at the legs for mottling and swelling
Teach to rise slowly to avoid dizziness

Pregnancy and breastfeeding

Human data are limited; use in pregnancy is a specialist decision.

Test yourself

Think of the answer, then tap the question to see it.

For which complication of levodopa therapy is amantadine mainly used?

Levodopa-induced dyskinesia.

Which skin finding is typical of amantadine?

Livedo reticularis, a mottled purplish pattern on the legs, often with ankle oedema.

Why is amantadine no longer recommended for influenza?

Circulating influenza A viruses have high levels of resistance to the adamantanes.

Why must the dose be reduced in kidney failure?

It is excreted mainly unchanged in the urine and accumulates, with toxicity that can be fatal.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - AMANTADINE HYDROCHLORIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); Amantadine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023); Influenza Antiviral Medications: Summary for Clinicians (Centers for Disease Control and Prevention, 2025).

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Representative model, for educational purposes only.