Amantadine may improve PD by releasing dopamine from the neurons in the substantia nigra, or by blocking the production of acetylcholine. Drugs that block acetylcholine increase the activity of dopamine. Side effects of amantadine include a reddish-violet discoloration of the legs called “livedo reticularis.” This may be accompanied by swelling, but the discoloration and swelling disappear when amantadine is stopped. In older people (age 70 plus) amantadine may cause hallucinations, but again, the hallucinations stop when amantadine is stopped.
It has been found that amantadine decreases levodopa-induced dyskinesia. The effect on dyskinesia is related to amantadine’s ability to block a type of receptor called an NMDA receptor, a receptor for the amino acid glutamate. Glutamate is involved in exciting, rather than inhibiting, blocking, or depressing nerve cells. However, too much glutamate, like too much excitement, isn’t good. NMDA receptors hook onto glutamate and let it do its work of exciting the cell, but these NMDA receptors may become overly sensitive, which results in dyskinesia. By blocking the NMDA receptors, amantadine decreases dyskinesia.