Amantadine for the Treatment of Parkinson’s Disease and its Associated Dyskinesias

Abstract

Disturbances of motor function characteristic of Parkinson’s Disease (PD) are commonly treated with L-Dopa. However, prolonged treatment commonly results in L-Dopa-Induced Dyskinesias (LIDs) with high negative impact on patient’s quality of life that seriously limits the use of L-Dopa. Amantadine, like L-Dopa, is effective for the replenishment of defective dopamine production in PD by mechanisms involving increased synthesis and decreased synaptic reuptake with consequent improvements of the patient’s motor symptoms. Results of RCTs and meta-analyses continue to support the claim that amantadine is effective for the treatment of early or stable PD. Preclinical and clinical studies reveal that LIDs result from modifications of corticostriatal (glutamatergic) and nigrostrial (dopaminergic) connectivity resulting from the relative over-activation of NMDA receptors, a phenomenon shown to occur in patients with LIDs using Positron Emission Tomography. In addition to its beneficial actions in restoring dopaminergic function, amantadine is a potent non-competitive NMDA receptor antagonist and, as such, affords a potentially effective agent for the treatment for LIDs. Indeed, beneficial effects of amantadine for the treatment of LIDs have been described in multiple Randomized Controlled Trials (RCTs) using a range of wellestablished dyskinesia rating scales over the last two decades and extended-release formulations of amantadine have also been found to be effective. Confirmation of clinical efficacy of amantadine for the treatment of LIDs has been complemented by the results of systematic reviews and meta-analyses that include a Movement Disease Society (MDS)-commissioned evidence-based update of treatment options. Treatment of PD patients with amantadine during the COVID-19 pandemic could be advantageous since, in addition to its ability to correct the movement disorder and dyskinesias, amantadine has the potential to limit replication of SARS-CoV-2, the virus responsible for COVID-19.