# No New Relevant Treatment Options for L-DOPA-Induced Dyskinesia from a Clinician’s Point of View

## TL;DR

This paper reviews treatment options for dyskinesia in Parkinson’s disease, concluding that few new therapies have emerged beyond amantadine.

## Contribution

The paper highlights the lack of new clinically approved treatments for L-DOPA-induced dyskinesia despite experimental research advances.

## Key findings

- Amantadine is the only drug with a new mode of action that has shown moderate success in reducing dyskinesia.
- Experimental research has not consistently translated into successful clinical trials for new antidyskinetic drugs.
- Continuous dopamine receptor stimulation remains a key strategy, but new approaches have largely failed in clinical settings.

## Abstract

Background: The term dyskinesia describes involuntary movements of the face, body and extremities. Frequently, they appear following and in relation with prior oral long-lasting and high-dose levodopa therapy in Parkinson’s disease patients. Onset of these motion sequences causes patient distress and caregiver embarrassment with declined quality of life. Continuity of nigrostriatal postsynaptic dopamine receptor stimulation delays occurrence of dyskinesia. A pulsatile pattern with temporary too high dopamine receptor excitation promotes manifestation of dyskinesia. Methods: This narrative review describes past pharmacologic approaches for therapy of dyskinesia, such as the principle of continuous dopamine receptor stimulation. Discussion and Conclusions: Novel concepts were tested. They influenced neurotransmission of serotonin and altered stimulation of dopamine receptor subtypes. The translation of successful experimental research outcomes into valuable clinical trial results with consecutive approval of drugs with a new mode of action under the indication “antidyskinetic” repeatedly failed. An exception is the open-channel blocker of the N-methyl-D-aspartate receptor and dopamine reuptake inhibitor amantadine with its moderate dyskinesia-reducing effects, particularly in its extended-release formulation. This antiviral compound also improves impaired motor behavior and reduces “OFF” intervals. Therefore, amantadine is currently experiencing a certain resurgence in regions where its extended-release formulations are marketed for therapy of levodopa-induced dyskinesia.