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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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
Sulochana, Devi +6 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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Metabotropic Glutamate Receptor 5 Upregulation in A-Fibers after Spinal Nerve Injury: 2-Methyl-6-(Phenylethynyl)-Pyridine (MPEP) Reverses the Induced Thermal Hyperalgesia [PDF]
The Journal of Neuroscience, 2002 Metabotropic glutamate receptor 5 (mGluR5) protein increased after sciatic nerve section in ipsilateral L4 and L5 DRG neuronal profiles, with most of the increase occurring in myelinated A-fiber somata. mGluR5 also increased in lamina II of the ipsilateral spinal cord and the proximal sciatic nerve stump in this model.
Lindsey J, Hudson +6 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.
Anuradha, Dhingra +4 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 ...
Y, Tagawa +4 more
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ACS Medicinal Chemistry LettersThis Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu5) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise,
Elizabeth S. Childress +20 more
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Involvement of metabotropic glutamate receptor 5, AKT/PI3K Signaling and NF-κB pathway in methamphetamine-mediated increase in IL-6 and IL-8 expression in astrocytes [PDF]
Journal of Neuroinflammation, 2012 Methamphetamine (MA) is one of the commonly used illicit drugs and the central nervous system toxicity of MA is well documented. The mechanisms contributing to this toxicity have not been fully elucidated.
Shah Ankit +3 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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