L-Dopa-induced dyskinesias ( LID ) are the most common adverse effects of long-term dopaminergic therapy in Parkinson's disease ( PD ). However, the exact mechanisms underlying dyskinesia are still unclear.

For a long time, nigrostriatal degeneration and pulsatile stimulation of striatal postsynaptic receptors have been highlighted as the key factors for the development of L-Dopa-induced dyskinesias.
In recent years, PD models have revealed a wide range of non-dopaminergic neurotransmitter systems involved in pre- and postsynaptic changes and thereby contributing to the pathophysiology of L-Dopa-induced dyskinesias.

Researchers have focused on therapeutic LID targets, mainly based on agents acting on dopaminergic, glutamatergic, serotoninergic, adrenergic, and cholinergic systems.

Despite a large number of clinical trials, currently only Amantadine and, to a lesser extent, Clozapine are being used as effective strategies in the treatment of L-Dopa-induced dyskinesias in clinical settings.

News drugs in development

Promising results include the extension of L-dopa action without inducing L-Dopa-induced dyskinesias of the novel monoamine oxidase B- and glutamate-release inhibitor Safinamide; however, this had no obvious effect on existing L-Dopa-induced dyskinesias.

Others, like the metabotropic glutamate-receptor antagonist AFQ056, have shown promising results in some of the studies; however, confirmation is still lacking.

Thus, to date, strategies of continuous dopaminergic stimulation seem the most promising to prevent or ameliorate L-Dopa-induced dyskinesias. ( Xagena )

Schaeffer E, Pilotto A, Berg D, CNS Drugs 2014;28:1155-1184

XagenaMedicine2014