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Journal of Neural Transmission

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31.01.2018 | Neurology and Preclinical Neurological Studies - Original Article

Glutamatergic mechanisms in l-DOPA-induced dyskinesia and therapeutic implications

verfasst von: Manuela Mellone, Fabrizio Gardoni

Erschienen in: Journal of Neural Transmission | Ausgabe 8/2018

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Abstract

Overactivation of the glutamatergic synapse leading to maladaptive synaptic plasticity in the basal ganglia is a well-demonstrated process involved in the onset of l-DOPA-induced dyskinesia (LID). Changes in glutamate release are paralleled by compensatory modifications of the expression and/or synaptic localization of both ionotropic and metabotropic glutamate receptors (mGluRs). Accordingly, compounds targeting N-methyl-d-aspartate glutamate receptors (NMDARs) and specific subtypes of metabotropic glutamate receptors (mGluR4 and mGluR5) have been tested both in preclinical and clinical studies. At present, amantadine, a low-affinity non-competitive NMDAR antagonist, represents the only recommended add-on agent with a moderate anti-dyskinetic activity. The present review describes recent advances in basic research, preclinical and early clinical studies in the attempt of identifying innovative strategies for an accurate modulation of both pre- and postsynaptic glutamate receptors to reduce the severity of LID. Even if a complete understanding of LID molecular bases is still lacking, several compounds demonstrated an anti-dyskinetic activity in preclinical and early clinical studies. These results indicate that modulation of the glutamatergic system remains one of the most promising pharmacological strategies in the field.

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Titel: Glutamatergic mechanisms in l-DOPA-induced dyskinesia and therapeutic implications
verfasst von: Manuela Mellone
Fabrizio Gardoni
Publikationsdatum: 31.01.2018
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 8/2018
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-018-1846-8

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Glutamatergic mechanisms in l-DOPA-induced dyskinesia and therapeutic implications

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