Targeting metabotropic glutamate receptors (mGluRs) in Parkinson's disease


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Abstract

HighlightsGlutamatergic transmission is increased in Parkinson's disease.mGlu receptor drugs are modulators of excessive glutamate and GABA transmission in the basal ganglia.Potential beneficial effects of mGlu5 receptor antagonists on l-DOPA-induced dyskinesia.Therapeutic potential of mGlu receptor modulation of nonmotor symptoms of Parkinson's disease.The interplay between dopamine and glutamate in the basal ganglia regulate critical aspects of motor and cognitive behavior. Metabotropic glutamate (mGlu) receptors are key modulators of glutamatergic dysfunction in Parkinson's disease (PD). Preclinical evidence demonstrate that group I mGlu receptor antagonism and groups II and III mGlu receptor activation improve motor symptomatology of PD and decrease l-DOPA-induced dyskinesia by regulating excitatory and inhibitory transmission in the basal ganglia. Emotional and cognitive deficits are also observed in PD. Treatment of these symptoms is challenging and underscore the need for novel effective and well tolerated pharmacological treatments. This article will thus review the currently available knowledge regarding the therapeutic potential of targeting mGlu receptors to restore motor and nonmotor symptoms of PD.

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