Current Medicinal Chemistry

Author(s): Zsófia Majláth, József Toldi, Ferenc Fülöp and László Vécsei

DOI: 10.2174/0929867323666160212121915

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Excitotoxic Mechanisms in Non-Motor Dysfunctions and Levodopa- Induced Dyskinesia in Parkinson's Disease: The Role of the Interaction Between the Dopaminergic and the Kynurenine System

Page: [874 - 883] Pages: 10

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Abstract

Parkinson’s disease is a common progressive neurodegenerative disorder presenting with characteristic motor symptoms. Non-motor dysfunctions and therapyrelated complications frequently develop, but are often underdiagnosed and undertreated. Levodopa- induced dyskinesia and impulse control disorders are suggested to share pathophysiological processes and m a y be related to alterations of the glutamatergic neurotransmission. Anti- glutamatergic interventions are therefore worth considering: several lines of evidence already indicate their beneficial effect. The kynurenine pathway offers the endogenous glutamate receptor antagonist kynurenic acid, which may act as a promising candidate for future drug development with the aim of assessment of the motor symptoms and therapy-related complications of Parkinson’s disease.

Keywords: Parkinson’s disease, kynurenic acid, neuroprotection, NMDA receptor, glutamate, levodopa-induced dyskinesia, excitotoxicity.