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CNS Drugs

, Volume 9, Issue 6, pp 421–429 | Cite as

Glutamate Antagonists for Parkinson’s Disease

Rationale for Use and Therapeutic Implications
  • Alison J. Cooper
  • Camille B. Carroll
  • Ian J. Mitchell
Leading Article

Abstract

Parkinson’s disease results from degeneration of dopaminergic neurons within the substantia nigra. The treatment of the disease was revolutionised by the introduction of dopamine replacement therapy. However, it has become increasingly clear that prolonged administration of dopamine agonists results in the onset of a spectrum of serious adverse effects, including dyskinesias. Accordingly, there is great interest in alternative strategies for the treatment of this condition. It is now realised that the loss of nigral dopamine cells and subsequent lowering of striatal dopamine levels causes a chain of pathophysiological events within the basal ganglia. One of the most prominent of these events is an elevation in the level of glutamate-mediated transmission within the striatum and the output structures of the basal ganglia.

A range of glutamate antagonists has been shown to alleviate symptoms in animal models of Parkinson’s disease. Antagonists of both the N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtypes of the glutamate receptor result in an improvement in motor behaviour in experimental animal models. However, systemic administration of NMDA antagonists is also associated with several adverse effects, the most common being ataxia, sedation and cognitive impairments. These problems can potentially be overcome by the use of antagonists that are selective for the subtypes of NMDA receptors which are preferentially expressed in the critical parts of the pathophysiological circuitry.

Glutamate antagonists are also known to have strong neuroprotective effects. Consequently, administration of glutamate antagonists may slow the rate of loss of nigral dopaminergic neurons and thus slow the progression of Parkinson’s disease.

Keywords

NMDA NMDA Receptor Globus Pallidus NMDA Receptor Antagonist NMDA Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Adis International Limited 1998

Authors and Affiliations

  • Alison J. Cooper
    • 1
  • Camille B. Carroll
    • 2
  • Ian J. Mitchell
    • 2
  1. 1.Department of PharmacologyUniversity of BirminghamEdgbastonEngland
  2. 2.School of Psychology, University of BirminghamEdgbastonEngland

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