What are the contraindications to prescribing amantadine?

Amantadine is not recommended for pronounced cognitive impairment with a risk of psychosis. The decision to prescribe is made only after neuropsychological testing and evaluation of cognitive status.

What are the pharmacokinetic features of amantadine?

Pharmacokinetic features of amantadine include a high degree of absorption when taken orally. The drug is intended for oral administration after meals, with a bioavailability exceeding 90%. Unlike its derivative rimantadine, which exhibits intensive metabolism and a long half-life, the pharmacokinetics of amantadine in sources is described briefly, limited to indicators of high bioavailability.

What antiparkinsonian drug groups is amantadine combined with?

Amantadine is used in combination with levodopa. Sources also mention the combination of amantadine with an anticholinergic agent in case of insufficient efficacy of monotherapy.

What symptoms characterize acute amantadine overdose?

Amantadine intoxication can trigger hallucinatory-delusional psychoses with schizophreniform symptoms.

Why doesn't amantadine treat drug-induced parkinsonism?

Drug-induced parkinsonism is most commonly caused by the direct blockade of dopamine receptors by neuroleptics, so increasing dopamine release via amantadine cannot overcome this receptor blockade.

What is the neuroprotective action of the drug?

It blocks NMDA receptors on neurons of the substantia nigra, preventing calcium ions from entering the cell in excessive amounts, which prevents excitotoxicity.

What is the main problem with long-term amantadine use?

The main problem is the rapid development of tolerance, due to which the therapeutic antiparkinsonian effect decreases over time.

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Amantadine

Amantadinum

For medical students2 min readUpdated 2026-10-10

Amantadine is an antiparkinsonian drug with a mixed mechanism of action that simultaneously affects the dopaminergic and glutamatergic systems of the central nervous system. The agent helps correct neurotransmitter imbalance in the basal ganglia and demonstrates moderate clinical efficacy.

Site of ActionNeostriatum and substantia nigra

Therapeutic FeatureRapid development of tolerance

LimitationIneffective in drug-induced parkinsonism

Mechanisms of Antiparkinsonian Action

The pharmacodynamics of amantadine is based on a complex, mixed effect on various neurotransmitter pools in the brain. There are three key components of its activity:

Direct dopaminergic mechanism. The drug stimulates the release of endogenous dopamine into the synaptic cleft. Important condition: the process occurs only from intact presynaptic terminals. Additionally, amantadine inhibits the neuronal reuptake of dopamine. As a result of these two processes, the concentration of dopamine in the CNS significantly increases, leading to a reduction in motor symptoms.
Antiglutamatergic mechanism. The drug acts as an antagonist, blocking NMDA receptors located on cholinergic neurons of the basal ganglia. This blockade prevents the excessive stimulatory action of glutamate. This leads to the suppression of cholinergic transmission in the neostriatum and allows for the effective correction of the pathological imbalance between dopamine and acetylcholine.
Anticholinergic mechanism. In addition to its indirect influence via the glutamate system, the molecule possesses its own, albeit moderately expressed, direct anticholinergic activity.

Neuroprotective Potential

In addition to symptomatic control, the drug has the ability to protect nerve cells from death. This neuroprotective effect is also realized through action on the glutamate system.

Amantadine blocks NMDA receptors localized directly on dopaminergic neurons of the substantia nigra. This blockade is critically important because it reduces the excessive influx of calcium ions ($Ca^{2+}$) into the cell. Preventing intracellular calcium overload reliably inhibits excitotoxicity, thereby slowing down neuronal degradation and death.

Clinical Profile and Safety

In clinical practice, the drug demonstrates a moderate antiparkinsonian effect.

Indications and Place in Therapy:

Prescribed for Parkinson's disease and various parkinsonian syndromes.
Exception: the drug is not used to treat drug-induced parkinsonism.
Often used in situations where levodopa is contraindicated, or prescribed in combination therapy with it to potentiate the effect.
Important course feature: tolerance to the drug develops relatively quickly, which manifests as a gradual decrease in its therapeutic effect.

Side Effects: Adverse reactions are associated with effects on various body systems:

CNS: patients may experience agitation, increased irritability, sleep disturbances (insomnia), and dizziness.
Autonomic and other disturbances: orthostatic hypotension may develop, and in severe cases, seizures.

Mnemonic

Remember amantadine's action via the formula "Plus dopamine, minus glutamate": it RELEASES dopamine from the presynapse and CLOSES NMDA receptors like a shield against calcium.

Frequently asked questions

What are the contraindications to prescribing amantadine?: Amantadine is not recommended for pronounced cognitive impairment with a risk of psychosis. The decision to prescribe is made only after neuropsychological testing and evaluation of cognitive status.
What are the pharmacokinetic features of amantadine?: Pharmacokinetic features of amantadine include a high degree of absorption when taken orally. The drug is intended for oral administration after meals, with a bioavailability exceeding 90%. Unlike its derivative rimantadine, which exhibits intensive metabolism and a long half-life, the pharmacokinetics of amantadine in sources is described briefly, limited to indicators of high bioavailability.
What antiparkinsonian drug groups is amantadine combined with?: Amantadine is used in combination with levodopa. Sources also mention the combination of amantadine with an anticholinergic agent in case of insufficient efficacy of monotherapy.
What symptoms characterize acute amantadine overdose?: Amantadine intoxication can trigger hallucinatory-delusional psychoses with schizophreniform symptoms.
Why doesn't amantadine treat drug-induced parkinsonism?: Drug-induced parkinsonism is most commonly caused by the direct blockade of dopamine receptors by neuroleptics, so increasing dopamine release via amantadine cannot overcome this receptor blockade.
What is the neuroprotective action of the drug?: It blocks NMDA receptors on neurons of the substantia nigra, preventing calcium ions from entering the cell in excessive amounts, which prevents excitotoxicity.
What is the main problem with long-term amantadine use?: The main problem is the rapid development of tolerance, due to which the therapeutic antiparkinsonian effect decreases over time.

Go deeper

Mechanisms of excitotoxicity and the role of calcium ions in neuronal death
Comparison of the efficacy of amantadine and levodopa preparations
Principles of combination therapy for Parkinson's disease
The role of neostriatal cholinergic neurons in motor control
Differences between the pathogenesis of Parkinson's disease and parkinsonism syndrome