Pharmacological Treatments Inhibiting Levodopa-Induced Dyskinesias in MPTP-Lesioned Monkeys: Brain Glutamate Biochemical Correlates

Overview

Journal Front Neurol

Specialty Neurology

Date 2014 Aug 21

PMID 25140165

Citations 12

Authors

Nicolas Morin

Therese Di Paolo

Affiliations

Soon will be listed here.

Abstract

Anti-glutamatergic drugs can relieve Parkinson's disease (PD) symptoms and decrease l-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)-lesioned monkeys. Antagonists of the ionotropic glutamate receptors, such as N-methyl-d-aspartate (NMDA) and α-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.

Citing Articles

Levodopa-induced dyskinesia: interplay between the N-methyl-D-aspartic acid receptor and neuroinflammation.

Zhang F, Liu M, Tuo J, Zhang L, Zhang J, Yu C Front Immunol. 2023; 14:1253273.

PMID: 37860013 PMC: 10582719. DOI: 10.3389/fimmu.2023.1253273.

AV-101, a Pro-Drug Antagonist at the NMDA Receptor Glycine Site, Reduces L-Dopa Induced Dyskinesias in MPTP Monkeys.

Bourque M, Gregoire L, Patel W, Dickens D, Snodgrass R, Di Paolo T Cells. 2022; 11(22).

PMID: 36428960 PMC: 9688762. DOI: 10.3390/cells11223530.

Molecular Mechanisms and Therapeutic Strategies for Levodopa-Induced Dyskinesia in Parkinson's Disease: A Perspective Through Preclinical and Clinical Evidence.

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Tyrosinyl-amantadine: A New Amantadine Derivative With an Ameliorative Effect in a 6-OHDA Experimental Model of Parkinson's Disease in Rats.

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PMID: 35091981 DOI: 10.1007/s12031-021-01964-x.

Pathophysiological Mechanisms and Experimental Pharmacotherapy for L-Dopa-Induced Dyskinesia.

Fabbrini A, Guerra A J Exp Pharmacol. 2021; 13:469-485.

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