ArticleACS chemical neuroscience2016
Development and Antiparkinsonian Activity of VU0418506, a Selective Positive Allosteric Modulator of Metabotropic Glutamate Receptor 4 Homomers without Activity at mGlu2/4 Heteromers.
Article in ACS chemical neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 58 citations in OpenAlex.
- Discovery of VU6081679, a Novel Positive Allosteric Modulator of Metabotropic Glutamate Receptor 8 with Efficacy in a Preclinical Model of Parkinson's Disease.ACS chemical neuroscience · 2026Article
- Targeting metabotropic glutamate receptors for symptomatic and disease-modifying treatment in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Potentiation of group III metabotropic glutamate receptors positively affects neurophysiological features in a mouse model of Rett syndrome.The Journal of pharmacology and experimental therapeutics · 2025Article
- Update on mGlu4 modulator patents: 2017 to present.Expert opinion on therapeutic patents · 2025Review
- Elucidating the molecular logic of a metabotropic glutamate receptor heterodimer.Nature communications · 2024Article
- Advances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging.Journal of medicinal chemistry · 2024Review
- Pyrazolopyridine-based kinase inhibitors for anti-cancer targeted therapy.RSC medicinal chemistry · 2024Review
- Cholesterol in Class C GPCRs: Role, Relevance, and Localization.Membranes · 2023Article
- Regulation and functional consequences of mGluRNA (New York, N.Y.) · 2021Article
- A nanobody activating metabotropic glutamate receptor 4 discriminates between homo- and heterodimers.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Input-specific regulation of glutamatergic synaptic transmission in the medial prefrontal cortex by mGluScience signaling · 2021Article
- Putative mGluR4 positive allosteric modulators activate GNeurochemistry international · 2020Article
- Synthesis and pharmacological evaluation of bivalent tethered ligands to target the mGluBioorganic & medicinal chemistry letters · 2020Article
- Synthesis and Characterization of Fluorine-18-LabeledJournal of medicinal chemistry · 2020Article
- Challenges in the Discovery and Optimization of mGluLetters in drug design & discovery · 2019Article
- Neuropharmacological Insight from Allosteric Modulation of mGlu Receptors.Trends in pharmacological sciences · 2019Review
- Discovery of VU2957 (Valiglurax): An mGluACS medicinal chemistry letters · 2019Article
- Glutamatergic mechanisms in L-DOPA-induced dyskinesia and therapeutic implications.Journal of neural transmission (Vienna, Austria : 1996) · 2018Article
- Self-Organized Nanostructure Modified Microelectrode for Sensitive Electrochemical Glutamate Detection in Stem Cells-Derived Brain Organoids.Biosensors · 2018Article
- Allosteric control of an asymmetric transduction in a G protein-coupled receptor heterodimer.eLife · 2017Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Metabotropic glutamate receptor 4 (mGlu4) is emerging as a potential therapeutic target for numerous central nervous system indications, including Parkinson's disease (PD). As the glutamate binding sites among the eight mGlu receptors are highly conserved, modulation of receptor activity via allosteric sites within the receptor transmembrane domains using positive and negative allosteric modulators (PAMs and NAMs, respectively) has become a common strategy. We and others have used PAMs targeting mGlu4 to show that potentiation of receptor signaling induces antiparkinsonian activity in a variety of PD animal models, including haloperidol-induced catalepsy and 6-hydroxydopamine-induced lesion. Recently, mGlu4 has been reported to form heteromeric complexes with other mGlu receptor subtypes, such as mGlu2, and the resulting heteromer exhibits a distinct pharmacological profile in response to allosteric modulators. For example, some mGlu4 PAMs do not appear to potentiate glutamate activity when mGlu2 and mGlu4 are coexpressed, whereas other compounds potentiate mGlu4 responses regardless of mGlu2 coexpression. We report here the discovery and characterization of VU0418506, a novel mGlu4 PAM with activity in rodent PD models. Using pharmacological approaches and Complemented Donor-Acceptor resonance energy transfer (CODA-RET) technology, we find that VU0418506 does not potentiate agonist-induced activity when mGlu2 and mGlu4 are heterodimerized, suggesting that the antiparkinsonian action of mGlu4 PAMs can be induced by compounds without activity at mGlu2/4 heteromers.
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