PD (Parkinson's disease) is characterized by some typical motor features that are caused by striatal dopamine depletion and respond well to dopamine-replacement therapy with L-dopa. Unfortunately, the majority of PD patients treated with L-dopa develop abnormal involuntary movements (dyskinesias) within a few years. The mechanisms underlying the development of LIDs (L-dopa-induced dyskinesias) involve, on one hand, a presynaptic dysregulation of dopamine release and clearance and, on the other hand, an abnormal postsynaptic response to dopamine in the brain. There is a large amount of evidence that these dopamine-dependent mechanisms are modulated by glutamatergic pathways and glutamate receptors. The present article summarizes the pathophysiological role of glutamatergic pathways in LID and reviews pre-clinical and clinical results obtained using pharmacological modulators of different classes and subtypes of glutamate receptors to treat parkinsonian dyskinesias.
- drug-induced movement disorder
- glutamatergic pathway
- neurodegenerative disease
- Parkinson’s disease
Brain Disorders Across the Lifespan: Translational Neuroscience from Molecule to Man: An Independent Meeting held at University College Cork, Ireland, 12–13 September 2013. Organized and Edited by Eoin Fleming (University College Cork, Ireland).
Abbreviations: AMPA, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; iGluR, ionotropic glutamate receptor; LID, L-dopa-induced dyskinesia; mGluR, metabotropic glutamate receptor; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NMDA, N-methyl-D-aspartate; 6-OHDA, 6-hydroxydopamine; PAM, positive allosteric modulator; PD, Parkinson’s disease; PET, positron-emission tomography; STN, subthalamic nucleus
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