Discovery of 4-alkoxy-6-methylpicolinamide negative allosteric modulators of metabotropic glutamate receptor subtype 5 [PDF]
Bioorganic & Medicinal Chemistry Letters, 2018 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.
Andrew S. Felts +11 more
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Expression and functional characterization of Metabotropic Glutamate Receptor Type 6 (mGluR6) in detergent micelles [PDF]
Biophysical Journal, 2009 Metabotropic glutamate receptors (mGluRs) are G protein coupled receptors which are implicated in different brain functions and dysfunctions including learning, memory, pain perception, neurodegeneration, schizophrenia and addiction. Metabotropic glutamate receptor type 6 (mGluR6) is a subtype of mGluRs which is exclusively expressed in ON-bipolar ...
Kalyan Tirupula +3 more
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Chronic interleukin‐6 exposure alters metabotropic glutamate receptor‐activated calcium signalling in cerebellar Purkinje neurons [PDF]
European Journal of Neuroscience, 2004 AbstractChronic central nervous system expression of the cytokine interleukin‐6 (IL‐6) is thought to contribute to the histopathological, pathophysiological, and cognitive deficits associated with various neurological disorders. However, the effects of chronic IL‐6 expression on neuronal function are largely unknown.
Thomas E. Nelson +2 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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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 ...
Kalyan Tirupula
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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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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
José Luís Albasanz +5 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.
Andrew S. Felts +9 more
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Molecular docking studies of N-substituted 4-methoxy-6-oxo-1-aryl-pyridazine-3-carboxamide derivatives as potential modulators of glutamate receptors [PDF]
Research Results in Pharmacology, 2020 Introduction: The virtual target-oriented screening is a necessary stage of modern drug-design. In the present study, the affinity of pyridazine derivatives for the most promising antiparkinsonian biotargets – I–III groups of metabotropic and ionotropic ...
Hanna I. Severina +5 more
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Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice [PDF]
PeerJ, 2015 Spinal astrocyte activation contributes to the pathogenesis of paclitaxel-induced neuropathic pain (PINP) in animal models. We examined glial fibrillary acidic protein (GFAP; an astrocyte marker) immunoreactivity and gene expression of GFAP, glutamate ...
Willias Masocha
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