Discovery of 4-alkoxy-6-methylpicolinamide negative allosteric modulators of metabotropic glutamate receptor subtype 5 [PDF]
Bioorganic & Medicinal Chemistry Letters, 2019 This letter describes the further chemical optimization of VU0424238 (auglurant), an mGlu5 NAM clinical candidate that failed in non-human primate (NHP) 28 day toxicology due to accumulation of a species-specific aldehyde oxidase (AO) metabolite of the pyrimidine head group.
J. Scott Daniels +12 more
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Role of Conserved Transmembrane Domain Cysteines in Activation of Metabotropic Glutamate Receptor Subtype 6 [PDF]
Medicinal chemistry, 2012 Metabotropic glutamate receptor subtype 6 (mGluR6) is a Class C type G protein coupled receptor (GPCR) uniquely expressed on retinal bipolar cells. mGluR6 plays a key role in dim-light vision but little is known about its structure and function. Here, we characterized the role of the three transmembrane (TM) cysteines in activation through site ...
ro Bisello +5 more
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Protective effect of metabotropic glutamate mGluR5 receptor elimination in a 6-hydroxydopamine model of Parkinson's disease [PDF]
Neuroscience Letters, 2010 Pharmacologic or genetic blockade of metabotropic glutamate mGlu5 receptors (mGluR5) has been shown to attenuate parkinsonian motor deficits and protect nigrostriatal neurons from damage in the acute MPTP model of Parkinson's disease (PD), suggesting that therapeutically targeting the mGluR5 receptor may offer a novel approach to improving motor ...
Yolanda D. Black +5 more
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A Retinal-Specific Regulator of G-Protein Signaling Interacts with Gαoand Accelerates an Expressed Metabotropic Glutamate Receptor 6 Cascade [PDF]
The Journal of Neuroscience, 2004 Gois the most abundant G-protein in the brain, but its regulators are essentially unknown. In retina, Gαo1is obligatory in mediating the metabotropic glutamate receptor 6 (mGluR6)-initiated ON response. To identify the interactors of Go, we conducted a yeast two-hybrid screen with constituitively active Gαoas a bait.
Eva Faurobert +4 more
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Discovery of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5 [PDF]
Bioorganic & Medicinal Chemistry Letters, 2018 Based on previous work that established fused heterocycles as viable alternatives for the picolinamide core of our lead series of mGlu5 negative allosteric modulators (NAMs), we designed a novel series of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide mGlu5 NAMs.
Anna L. Blobaum +10 more
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Immunohistological Studies of Metabotropic Glutamate Receptor Subtype 6-Deficient Mice Show No Abnormality of Retinal Cell Organization and Ganglion Cell Maturation [PDF]
The Journal of Neuroscience, 1999 Immature retinal ganglion cells (RGCs) initially show a multistratified dendritic pattern, and, during the postnatal period, these dendrites gradually monostratify into ON and OFF sublaminae. The selective agonist of group III metabotropic glutamate receptors (mGluR),l-2-amino-4-phosphonobutyrate (l-AP-4), hyperpolarizes ON bipolar cells and reduces ...
Yoshiaki Tagawa +4 more
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Metabotropic glutamate receptor 6 signaling enhances
Pigment Cell & Melanoma Research, 2013 SummaryMutations in TRPM1, a calcium channel expressed in retinal bipolar cells and epidermal melanocytes, cause complete congenital stationary night blindness with no discernible skin phenotype. In the retina, TRPM1 activity is negatively coupled to metabotropic glutamate receptor 6 (mGluR6) signaling through Gαo and TRPM1 mutations result in the loss
Noga Vardi +6 more
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ACS Chemical Neuroscience, 2019 As part of the G-protein coupled receptor (GPCR) family, metabotropic glutamate (mGlu) receptors play an important role as drug targets of cognitive diseases. Selective allosteric modulators of mGlu subtype 5 (mGlu5) have the potential to alleviate symptoms of numerous central nervous system disorders such as schizophrenia in a more targeted fashion ...
Mariusz Butkiewicz +8 more
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2-Methyl-6-(phenylethynyl)pyridine Hydrochloride Modulates Metabotropic Glutamate 5 Receptors Endogenously Expressed in Zebrafish Brain [PDF]
ACS Chemical Neuroscience, 2016 Due to phylogenetic proximity to the human, zebrafish has been recognized as a reliable model to study Alzheimer's disease (AD) and other central nervous system disorders. Furthermore, metabotropic glutamate receptors have been previously reported to be impaired in brain from AD patients. Metabotropic glutamate 5 (mGlu5) receptors are G-protein coupled
Albasanz, José Luis +5 more
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Journal of the Neurological SciencesImaging of type 1 metabotropic glutamate receptor (mGluR1), which is predominantly expressed in Purkinje cells, is currently possible using positron emission tomography (PET). We have previously shown that cerebellar mGluR1 availability decreases in patients with cerebellar ataxia and that the degree of ataxia is related to the magnitude of cerebellar ...
Yoshiharu, Miura, Kenji, Ishibashi
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