期刊
FRONTIERS IN NEUROLOGY
卷 5, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2014.00144
关键词
Parkinson's disease; L-DOPA-induced dyskinesia; motor complications; glutamate receptor; basal ganglia; direct pathway; indirect pathway; receptor interaction
资金
- Canadian Institutes of Health Research
- Fonds de la Recherche en Sante du Quebec
Anti-glutamatergic drugs can relieve Parkinson's disease (PD) symptoms and decrease 1-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (LID). This review reports relevant studies investigating glutamate receptor subtypes in relation to motor complications in PD patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Iesioned monkeys. Antagonists of the ionotropic glutamate receptors, such as N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, display antidyskinetic activity in PD patients and animal models such as the MPTP monkey. Metabotropic glutamate 5 (mGlu5) receptor antagonists were shown to reduce the severity of LID in PD patients as well as in already dyskinetic non-human primates and to prevent the development of LID in de novo treatments in non-human primates. An increase in striatal post-synaptic NMDA, AMPA, and mGlu5 receptors is documented in PD patients and MPTP monkeys with LID. This increase can be prevented in MPTP monkeys with the addition of a specific glutamate receptor antagonist to the L-DOPA treatment and also with drugs of various pharmacological specificities suggesting multiple receptor interactions. This is yet to be well documented for presynaptic mGlu4 and mGlu2/3 and offers additional new promising avenues.
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