Metabotropic Glutamate Receptors for Parkinson's Disease Therapy
Excessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson’s disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2013/196028 |
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| author | Fabrizio Gasparini Thérèse Di Paolo Baltazar Gomez-Mancilla |
| author_facet | Fabrizio Gasparini Thérèse Di Paolo Baltazar Gomez-Mancilla |
| author_sort | Fabrizio Gasparini |
| collection | DOAJ |
| description | Excessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson’s disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate glutamatergic signalling via glutamate receptors, as treatments for PD and L-DOPA-induced dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate receptor antagonists showed antiparkinsonian and antidyskinetic activity, their clinical use was limited due to psychiatric adverse effects, with the exception of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor) modulators were considered to have a more favourable side-effect profile, and several agents have been studied in preclinical models of PD. The most promising results have been seen clinically with selective antagonists of mGlu5 receptor and preclinically with selective positive allosteric modulators of mGlu4 receptor. The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD. |
| format | Article |
| id | doaj-art-d632bb4eaa854cea89436f2063d90694 |
| institution | Kabale University |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-d632bb4eaa854cea89436f2063d906942025-02-03T05:54:02ZengWileyParkinson's Disease2090-80832042-00802013-01-01201310.1155/2013/196028196028Metabotropic Glutamate Receptors for Parkinson's Disease TherapyFabrizio Gasparini0Thérèse Di Paolo1Baltazar Gomez-Mancilla2Novartis Pharma AG, Novartis Institutes for BioMedical Research Basel, Forum 1, Novartis Campus, 4056 Basel, SwitzerlandNeuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, QC, G1V 4G2, CanadaNovartis Pharma AG, Novartis Institutes for BioMedical Research Basel, Forum 1, Novartis Campus, 4056 Basel, SwitzerlandExcessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson’s disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate glutamatergic signalling via glutamate receptors, as treatments for PD and L-DOPA-induced dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate receptor antagonists showed antiparkinsonian and antidyskinetic activity, their clinical use was limited due to psychiatric adverse effects, with the exception of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor) modulators were considered to have a more favourable side-effect profile, and several agents have been studied in preclinical models of PD. The most promising results have been seen clinically with selective antagonists of mGlu5 receptor and preclinically with selective positive allosteric modulators of mGlu4 receptor. The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD.http://dx.doi.org/10.1155/2013/196028 |
| spellingShingle | Fabrizio Gasparini Thérèse Di Paolo Baltazar Gomez-Mancilla Metabotropic Glutamate Receptors for Parkinson's Disease Therapy Parkinson's Disease |
| title | Metabotropic Glutamate Receptors for Parkinson's Disease Therapy |
| title_full | Metabotropic Glutamate Receptors for Parkinson's Disease Therapy |
| title_fullStr | Metabotropic Glutamate Receptors for Parkinson's Disease Therapy |
| title_full_unstemmed | Metabotropic Glutamate Receptors for Parkinson's Disease Therapy |
| title_short | Metabotropic Glutamate Receptors for Parkinson's Disease Therapy |
| title_sort | metabotropic glutamate receptors for parkinson s disease therapy |
| url | http://dx.doi.org/10.1155/2013/196028 |
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