Glutamate receptors and levodopa-induced dyskinesia

Levodopa is considered the therapy of choice for Parkinson's disease (PD) treatment. After the early phases of the disease, in which levodopa treatment is highly effective against parkinsonian symptoms, uncontrolled motor fl uctuations and abnormal movements named levodopa-induced dyskinesia (LID) appears. An efficient antiparkinsonian/ antidyskinetic therapy has not so far been developed. Altered glutamatergic transmission is one of the main pathophysiological features of LID within basal ganglia circuit. Experimental evidence shows that the trafficking and the localization of the glutamate ionotropic (NMDA and AMPA) and metabotropic receptors in the synaptic cleft appear to have a relevant role in the pathogenesis of LID. Glutamate receptors have therefore been considered as potential targets for a novel pharmacological intervention in PD and LID treatment. Here we report an overview from the main preclinical studies in experimental models of PD and LID to the most recent clinical trials in PD patients describing the pros and cons of the use of glutamate receptor agents.