From the Guidelines
Amantadine is the agent used in Parkinson's Disease treatment that both enhances dopamine release from presynaptic nerve terminals and acts as a noncompetitive inhibitor of glutamate at NMDA receptors. This medication provides symptomatic relief in PD through its dual mechanism of action. By promoting dopamine release, amantadine helps compensate for the depleted dopamine levels characteristic of Parkinson's Disease. Simultaneously, its NMDA receptor antagonism modulates glutamatergic neurotransmission, which becomes dysregulated in PD. Amantadine is typically prescribed at doses of 100-300 mg daily, often starting at 100 mg once or twice daily and gradually increasing as needed. It can be used as monotherapy in early disease or as an adjunct to levodopa in more advanced cases, particularly to help manage levodopa-induced dyskinesias. Patients should be aware that common side effects include livedo reticularis (a purple mottling of the skin), ankle edema, confusion, and hallucinations, especially in elderly patients or those with renal impairment, so dosage adjustments may be necessary in these populations 1.
Some key points to consider when using amantadine include:
- Monitoring for side effects, particularly in vulnerable populations such as the elderly or those with renal impairment
- Gradually increasing the dose as needed and tolerated
- Considering the use of amantadine in combination with other therapies, such as levodopa, to manage symptoms and side effects
- Being aware of the potential for amantadine to interact with other medications, such as anticholinergics or other dopaminergic agents 1.
Overall, amantadine is a valuable treatment option for patients with Parkinson's Disease, offering both symptomatic relief and the potential to modulate glutamatergic neurotransmission. However, its use should be carefully considered and monitored, particularly in vulnerable populations.
From the FDA Drug Label
The mechanism of action of amantadine hydrochloride in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known Data from earlier animal studies suggest that amantadine hydrochloride may have direct and indirect effects on dopamine neurons. More recent studies have demonstrated that amantadine hydrochloride is a weak, non-competitive NMDA receptor antagonist (K = 10µM)
The agent used in the treatment of Parkinson's Disease (PD) that likely enhances dopamine (DA) release from presynaptic nerve terminals and is also a noncompetitive inhibitor of glutamate at N-methyl-D-aspartate (NMDA) receptors is amantadine 2.
- Key points:
- Amantadine may have direct and indirect effects on dopamine neurons.
- Amantadine is a weak, non-competitive NMDA receptor antagonist.
- The exact mechanism of action in PD is not fully understood.
From the Research
Agent Used in the Treatment of Parkinson's Disease
The agent used in the treatment of Parkinson's Disease (PD) that likely enhances dopamine (DA) release from presynaptic nerve terminals and is also a noncompetitive inhibitor of glutamate at N-methyl-D-aspartate (NMDA) receptors is:
- Amantadine, as it has been shown to increase dopamine synthesis and release in the striatum 3
Mechanism of Action
The mechanism of action of amantadine involves:
- Noncompetitive inhibition of NMDA receptors, which can provide a means of decreasing the abnormally increased activity of the subthalamic nucleus 4
- Enhancement of dopamine-induced stimulation of guanosine 5'-[gamma-35S]triphosphate ([35S]GTPgammaS) binding in rat striatal membranes 3
Comparison with Other Agents
In comparison with other agents used in the treatment of PD, such as:
- Levodopa, which is an effective and well-tolerated dopamine replacement agent, but may be associated with motor complications 5
- Dopamine agonists, which can provide useful alternatives to treatment with levodopa, but may have different side effects and efficacy profiles 6
- Monoamine oxidase B (MAO-B) inhibitors, which may have neuroprotective effects, but require further study to determine their long-term benefits 6 Amantadine has a unique mechanism of action that involves both enhancement of DA release and noncompetitive inhibition of glutamate at NMDA receptors, making it a potentially useful agent in the treatment of PD 4, 7, 3