Answer: Amantadine may produce central nervous system side effects such as dizziness, hallucinations, drowsiness, difficulty with impulse control, and suicidal ideation.

Levodopa therapy is the most efficient pharmacological therapy for treating the symptoms of Parkinson's disease (PD). People with PD experience issues with motor control, such as a resting tremor, bradykinesia (slowness of movement), and unsteady gait and posture. Giving levodopa, the biochemical precursor to the body's own dopamine, is an effective way to reverse the motor difficulties of the patients.

However, after long term treatment with levodopa, patients often begin to experience dyskinesia, uncontrolled movements such as tics and chorea. It is estimated that up to 80% of patients on levodopa therapy experience these dyskinesias after 5-10 years of treatment. In many cases, the dyskinesia can be more debilitating than the Parkinson's disease itself.

Currently, the only FDA-approved drug for treatment of dyskinesia is amantadine (Gocovri or Symmetrel), a drug originally developed as an antiviral. Amantadine has some effect as an anti-Parkinsonian medication, but this application is no longer used for this purpose. The oral preparation of amantadine is most effective when the blood concentration is maintained at a steady level, so patients benefit the most from dosing when they are evenly spaced apart and no doses are missed. The extended release capsules are usually taken before going to bed. There are also liquid preparations of the drug.

Mechanism of action

Pharmacologically, amantadine is a dirty drug. It's presumed main effect is as a glutamate NMDA receptor antagonist (Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study). Amantadine also functions to increase dopamine release and inhibit dopamine reuptake.

Amantadine also interacts with the cholinergic system. It blocks cholinergic signaling by acting as an antagonist of the alpha7 type nicotinic acetylcholine receptors. It is possible that this action contributes to the anti-dyskinetic property of the compound, if a hypercholinergic brain leads to dyskinesia.

Side effects of amantadine treatment

Amantadine is known to produce side effects such as hallucinations. These may be present because of amantadine's pharmacological action as an NMDA receptor antagonist.

Other minor side effects include dizziness, insomnia, and nausea. It’s not known exactly what causes these side effects.