ArticleNeuropharmacology2015
Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia: Comparison between a positive allosteric modulator and an orthosteric agonist.
Article in Neuropharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 50 citations in OpenAlex.
- Targeting metabotropic glutamate receptors for symptomatic and disease-modifying treatment in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Metabotropic Glutamate Receptor 4 (mGlu4) Positive Allosteric Modulators Lack Efficacy in Rat and Marmoset Models of L-DOPA-Induced Dyskinesia.Journal of Parkinson's disease · 2024Article
- Targeting Striatal Glutamate and Phosphodiesterases to Control L-DOPA-Induced Dyskinesia.Cells · 2023Review
- Effect of the mGluPsychopharmacology · 2023Article
- An Update on Nondopaminergic Treatments for Motor and Non-motor Symptoms of Parkinson's Disease.Current neuropharmacology · 2023Review
- Distinctive Effects of D1 and D2 Receptor Agonists on Cortico-Basal Ganglia Oscillations in a Rodent Model of L-DOPA-Induced Dyskinesia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Pathological and Therapeutic Advances in Parkinson's Disease: Mitochondria in the Interplay.Journal of Alzheimer's disease : JAD · 2023Review
- Molecular Mechanisms and Therapeutic Strategies for Levodopa-Induced Dyskinesia in Parkinson's Disease: A Perspective Through Preclinical and Clinical Evidence.Frontiers in pharmacology · 2022Review
- Review
- Roles of Glutamate Receptors in Parkinson's Disease.International journal of molecular sciences · 2019Review
- Receptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson's Disease.Biomolecules · 2019Review
- Role of Metabotropic Glutamate Receptors in Neurological Disorders.Frontiers in molecular neuroscience · 2019Article
- Glutamatergic mechanisms in L-DOPA-induced dyskinesia and therapeutic implications.Journal of neural transmission (Vienna, Austria : 1996) · 2018Article
- Ceftriaxone reduces L-dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson's disease model.Movement disorders : official journal of the Movement Disorder Society · 2017Article
- Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson's Disease.Chinese medical journal · 2017Review
- Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4.Bioorganic & medicinal chemistry letters · 2016Article
- Development of Novel, CNS Penetrant Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics.Journal of medicinal chemistry · 2015Article
- Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability.Bioorganic & medicinal chemistry letters · 2015Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Metabotropic glutamate receptor 4 (mGlu4) negatively modulates GABA and glutamate release in the 'indirect pathway' of the basal ganglia, and has thus been proposed as a potential target to treat motor symptoms in Parkinson's disease. Here, we present an extensive comparison of the behavioural effects produced by the mGlu4 positive allosteric modulator (PAM), VU0364770, and the mGlu4 orthosteric agonist, LSP1-2111, in rats with unilateral 6-OHDA lesions. The compounds' activity was initially assessed in a test of haloperidol-induced catalepsy in intact rats, and effective doses were then evaluated in the hemiparkinsonian animal model. Neither of the two compounds modified the development of dyskinetic behaviours elicited by chronic treatment with full doses of l-DOPA. When given together with l-DOPA to rats with already established dyskinesias, neither VU0364770 nor LSP1-2111 modified the abnormal involuntary movement scores. VU0364770 potentiated, however, the motor stimulant effect of a subthreshold l-DOPA dose in certain behavioural tests, whereas LSP1-2111 lacked this ability. Taken together, these results indicate that a pharmacological stimulation of mGlu4 lacks intrinsic antidyskinetic activity, but may have DOPA-sparing activity in Parkinson's disease. For the latter indication, mGlu4 PAMs appear to provide a better option than orthosteric agonists.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.