P Conn

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. ncbi mGluR7's lucky number
    P Jeffrey Conn
    Department of Pharmacology and Center for Translational Neuropharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 103:251-2. 2006
  2. ncbi Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA
    Zhijian Zhao
    Department of Medicinal Chemistry, Merck and Co, Inc, PO Box 4, West Point, PA 19486, USA
    Bioorg Med Chem Lett 17:1386-91. 2007
  3. ncbi Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists
    L Michelle Lewis
    Vanderbilt Program in Drug Discovery, Vanderbilt Institute of Chemical Biology, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:885-90. 2008
  4. ncbi Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides, sulfonamides and ureas--the effect of capping the distal basic piperidine nitrogen
    Nicole R Miller
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:5443-7. 2008
  5. ncbi Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity
    Joy E Marlo
    Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Mol Pharmacol 75:577-88. 2009
  6. ncbi Probing the Metabotropic Glutamate Receptor 5 (mGlu5) Positive Allosteric Modulator (PAM) Binding Pocket: Discovery of Point Mutations That Engender a "Molecular Switch" in PAM Pharmacology
    Karen J Gregory
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, 1215 Light Hall, 2215 B Garland Avenue, Nashville, TN 37232 0697
    Mol Pharmacol 83:991-1006. 2013
  7. ncbi A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling
    M J Noetzel
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Nashville, TN, USA
    Mol Pharmacol 83:835-47. 2013
  8. ncbi Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Mol Pharmacol 82:860-75. 2012
  9. ncbi Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, Nashville, TN 37232, USA
    Trends Pharmacol Sci 30:148-55. 2009
  10. ncbi Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Medical Center, Nashville, TN, USA
    Trends Pharmacol Sci 30:25-31. 2009

Research Grants

  1. REGULATION OF SIGNALING BY MGLUR5
    P Conn; Fiscal Year: 2005
  2. FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES
    P Jeffrey Conn; Fiscal Year: 2010
  3. mGluR4 Potentiators as a Treatment for Parkinson's Disease
    P Conn; Fiscal Year: 2007
  4. FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES
    P Conn; Fiscal Year: 2007
  5. Muscarinic receptor activators as novel antipsychotic agents
    P Conn; Fiscal Year: 2009
  6. Functional effects of mGluR potentiators in the CNS
    P Conn; Fiscal Year: 2009
  7. REGULATION OF SIGNALING BY MGLUR5
    P Conn; Fiscal Year: 2009
  8. Functional effects of mGluR potentiators in the CNS
    P Jeffrey Conn; Fiscal Year: 2010
  9. REGULATION OF SIGNALING BY MGLUR5
    P Jeffrey Conn; Fiscal Year: 2010
  10. Muscarinic receptor activators as novel antipsychotic agents
    P Jeffrey Conn; Fiscal Year: 2010

Collaborators

Detail Information

Publications95

  1. ncbi mGluR7's lucky number
    P Jeffrey Conn
    Department of Pharmacology and Center for Translational Neuropharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 103:251-2. 2006
  2. ncbi Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA
    Zhijian Zhao
    Department of Medicinal Chemistry, Merck and Co, Inc, PO Box 4, West Point, PA 19486, USA
    Bioorg Med Chem Lett 17:1386-91. 2007
    ..Binding to a unique allosteric binding site distinct from other mGluR5 PAMs, CPPHA has been the focus of numerous pharmacology studies by several laboratories...
  3. ncbi Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists
    L Michelle Lewis
    Vanderbilt Program in Drug Discovery, Vanderbilt Institute of Chemical Biology, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:885-90. 2008
    ..Compounds in this series possess M1 antagonist IC(50)s in the 441nM-19microM range with 8- to >340-fold functional selectivity versus rM2-rM5...
  4. ncbi Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides, sulfonamides and ureas--the effect of capping the distal basic piperidine nitrogen
    Nicole R Miller
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:5443-7. 2008
    ..Despite the large change in basicity and topology, M1 selectivity was maintained...
  5. ncbi Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity
    Joy E Marlo
    Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Mol Pharmacol 75:577-88. 2009
    ..These data also suggest that structurally diverse M(1) potentiators may act by distinct mechanisms and differentially regulate receptor coupling to downstream signaling pathways...
  6. ncbi Probing the Metabotropic Glutamate Receptor 5 (mGlu5) Positive Allosteric Modulator (PAM) Binding Pocket: Discovery of Point Mutations That Engender a "Molecular Switch" in PAM Pharmacology
    Karen J Gregory
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, 1215 Light Hall, 2215 B Garland Avenue, Nashville, TN 37232 0697
    Mol Pharmacol 83:991-1006. 2013
    ..Interestingly, we identified two point mutations in TMs 6 and 7 that, when mutated, engender a mode switch in the pharmacology of certain PAMs...
  7. ncbi A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling
    M J Noetzel
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Nashville, TN, USA
    Mol Pharmacol 83:835-47. 2013
    ..Such stimulus bias by mGlu5 PAMs may complicate drug discovery efforts but would also allow for specifically tailored therapies, if pharmacological biases can be attributed to different therapeutic outcomes...
  8. ncbi Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Mol Pharmacol 82:860-75. 2012
    ..This model can be applied to PAM and NAM potency curves in combination with maximal fold-shift data to derive reliable estimates of modulator affinities...
  9. ncbi Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, Nashville, TN 37232, USA
    Trends Pharmacol Sci 30:148-55. 2009
    ....
  10. ncbi Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Medical Center, Nashville, TN, USA
    Trends Pharmacol Sci 30:25-31. 2009
    ..These mGlu receptor-selective PAMs have properties needed for optimization as clinical candidates and have robust effects in animal models that predict efficacy in treatment of schizophrenia...
  11. ncbi Physiological roles and therapeutic potential of metabotropic glutamate receptors
    P Jeffrey Conn
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6600, USA
    Ann N Y Acad Sci 1003:12-21. 2003
    ..These studies suggest that drugs active at mGlu receptors may be useful in treatment of a wide variety of neurological and psychiatric disorders...
  12. ncbi Schizophrenia: moving beyond monoamine antagonists
    P Jeffrey Conn
    Vanderbilt University, Department of Pharmacology, Nashville, TN 37232, USA
    Mol Interv 8:99-107. 2008
    ..Current attempts to target a new range of receptors entail unprecedented fine-tuning in the pharmacological manipulation of specific receptor subtypes...
  13. ncbi Opportunities and challenges of psychiatric drug discovery: roles for scientists in academic, industry, and government settings
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    Neuropsychopharmacology 33:2048-60. 2008
    ..Also, increased attention should be focused on the development of early predictors of adverse effects of candidate compounds...
  14. ncbi Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, 1215 Light Hall, Nashville, Tennessee 37232, USA
    Nat Rev Drug Discov 8:41-54. 2009
    ..These compounds provide high selectivity, novel modes of efficacy and may lead to novel therapeutic agents for the treatment of multiple psychiatric and neurological human disorders...
  15. ncbi Functional impact of allosteric agonist activity of selective positive allosteric modulators of metabotropic glutamate receptor subtype 5 in regulating central nervous system function
    Meredith J Noetzel
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232 0697, USA
    Mol Pharmacol 81:120-33. 2012
    ..These data suggest that the level of receptor expression influences the ability of mGlu(5) PAMs to act as allosteric agonists in vitro and that ago-PAM activity observed in cell-based assays may not be important for in vivo efficacy...
  16. ncbi An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission
    Jana K Shirey
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, 23rd Avenue South at Pierce, Nashville, Tennessee 37232 6600, USA
    Nat Chem Biol 4:42-50. 2008
    ..Selective regulation of excitatory transmission by M4 suggests that targeting of individual mAChR subtypes could be used to differentially regulate specific aspects of mAChR modulation of function in this important forebrain structure...
  17. ncbi N-{4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide (CPPHA) acts through a novel site as a positive allosteric modulator of group 1 metabotropic glutamate receptors
    Yelin Chen
    Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 417 D Preston Research Building, Nashville, TN 37232 6600, USA
    Mol Pharmacol 73:909-18. 2008
    ..Together, these data suggest that CPPHA acts at a novel allosteric site on both mGluR1 and -5 to potentiate responses to activation of these receptors...
  18. ncbi Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, 802 Robinson Research Building, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:5439-42. 2008
    ..With slight structural changes, mAChR selectivity was maintained, but the degree of partial M1 agonism varied considerably...
  19. ncbi Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel mGluR4 positive allosteric modulators
    Colleen M Niswender
    Department of Pharmacology, Vanderbilt University Medical Center, 802 Robinson Research Building, Nashville, TN 37232 6600, USA
    Bioorg Med Chem Lett 18:5626-30. 2008
    ..Despite tremendous therapeutic potential, Compound 7, VU0080421, and related congeners represent only a handful of mGluR4 positive allosteric modulators ever described...
  20. ncbi A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors
    Kamondanai Hemstapat
    Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Pharmacol Exp Ther 322:254-64. 2007
    ..Our data suggest that these two positive allosteric modulators of mGluR2 may share a common binding site and that this site may be distinct from the binding site for the new negative allosteric modulators of group II mGluRs...
  21. ncbi Allosteric potentiators of metabotropic glutamate receptor subtype 1a differentially modulate independent signaling pathways in baby hamster kidney cells
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States
    Neuropharmacology 55:419-27. 2008
    ..Together, these data provide further evidence that allosteric compounds can differentially modulate the coupling of a single receptor to independent signaling pathways or act in a system-dependent manner...
  22. ncbi Synthesis and SAR of a mGluR5 allosteric partial antagonist lead: unexpected modulation of pharmacology with slight structural modifications to a 5-(phenylethynyl)pyrimidine scaffold
    Sameer Sharma
    Department of Pharmacology, Vanderbilt University Medical Center, 12415D MRBIV, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:4098-101. 2008
    ....
  23. ncbi A novel class of positive allosteric modulators of metabotropic glutamate receptor subtype 1 interact with a site distinct from that of negative allosteric modulators
    Kamondanai Hemstapat
    Department of Pharmacology, Vanderbilt University Medical Center, 23rd Ave. South at Pierce, 417-D Preston Research Bldg, Nashville, TN 37232-6600, USA
    Mol Pharmacol 70:616-26. 2006
    ..Site-directed mutagenesis revealed that valine at position 757 in transmembrane V of mGluR1a is crucial for the activity of multiple classes of allosteric mGluR1 potentiators...
  24. ncbi Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats
    Carrie K Jones
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6600, USA
    J Neurosci 28:10422-33. 2008
    ..Together, these data suggest that selective activation of M(1) may provide a novel approach for the treatment of symptoms associated with schizophrenia and Alzheimer's disease...
  25. ncbi Interaction of novel positive allosteric modulators of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor responses
    Yelin Chen
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    Mol Pharmacol 71:1389-98. 2007
    ....
  26. ncbi Allosteric potentiators of metabotropic glutamate receptor subtype 5 have differential effects on different signaling pathways in cortical astrocytes
    Yongqin Zhang
    Program in Translational Neuropharmacology, Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Pharmacol Exp Ther 315:1212-9. 2005
    ..Together, these data provide evidence that different allosteric potentiators can differentially modulate coupling of a single receptor to different signaling pathways...
  27. ncbi A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2/3 receptor agonist in mouse models predictive of antipsychotic activity
    Ruggero Galici
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 417-D Preston Research Building, Nashville, TN 37232-6600, USA
    J Pharmacol Exp Ther 315:1181-7. 2005
    ..Furthermore, these data raise the possibility that a selective allosteric potentiator of mGlu2 receptor could have utility as a novel approach for the treatment of schizophrenia...
  28. ncbi Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:558-62. 2010
    ..An iterative library synthesis approach delivered the first selective M(5) PAM (no activity at M(1)-M(4) @ 30microM), and an important tool compound to study the role of M(5) in the CNS...
  29. ncbi Synthesis and SAR of N-(4-(4-alklylpiperazin-1-yl)phenyl)benzamides as muscarinic acetylcholine receptor subtype 1 (M1) anatgonists
    Nicole R Miller
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:2174-7. 2010
    ..Compounds in this series possess M(1) antagonist IC(50)s in the 350 nM to >10 microM range with varying degrees of functional selectivity versus M(2)-M(5)...
  30. ncbi Allosteric modulation of metabotropic glutamate receptors: structural insights and therapeutic potential
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Neuropharmacology 60:66-81. 2011
    ..In the absence of a class C GPCR crystal structure, this approach has shown promise with respect to the interpretation of mutagenesis data and understanding structure-activity relationships of allosteric modulator pharmacophores...
  31. ncbi Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes
    Tomas de Paulis
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Med Chem 49:3332-44. 2006
    ..6 +/- 1.9 nM in the binding and functional assays, respectively...
  32. ncbi [(18)F]Fallypride dopamine D2 receptor studies using delayed microPET scans and a modified Logan plot
    Mohammed N Tantawy
    Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Nashville, TN 37232, USA
    Nucl Med Biol 36:931-40. 2009
    ..In particular, we applied a modified version of the Logan plot method on the last 60 min of 120-min data and compared the results to those from analysis of the full data set...
  33. ncbi Preclinical drug discovery research and training at Vanderbilt
    Craig W Lindsley
    Vanderbilt Institute of Chemical Biology Program in Drug Discovery, Department of Pharmacology, Vanderbilt Medical Center, Nashville, Tennessee 37232, USA
    ACS Chem Biol 2:17-20. 2007
  34. ncbi Allosteric activators of muscarinic receptors as novel approaches for treatment of CNS disorders
    Gregory J Digby
    Mol Biosyst 6:1345-54. 2010
    ..These novel allosteric modulators of mAChRs may provide therapeutic potential for treatment of a number of CNS disorders such as Alzheimer's disease and schizophrenia...
  35. ncbi Context-dependent pharmacology exhibited by negative allosteric modulators of metabotropic glutamate receptor 7
    Colleen M Niswender
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Mol Pharmacol 77:459-68. 2010
    ..The pharmacology of this compound represents a striking example of the potential for context-dependent blockade of receptor responses by negative allosteric modulators...
  36. ncbi Metabotropic glutamate receptors: physiology, pharmacology, and disease
    Colleen M Niswender
    Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37212, USA
    Annu Rev Pharmacol Toxicol 50:295-322. 2010
    ....
  37. ncbi A novel assay of Gi/o-linked G protein-coupled receptor coupling to potassium channels provides new insights into the pharmacology of the group III metabotropic glutamate receptors
    Colleen M Niswender
    1215 MRB IV, Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Mol Pharmacol 73:1213-24. 2008
    ..We anticipate that the GIRK-mediated thallium flux strategy will provide a novel tool to advance the study of G(i/o)-coupled GPCR biology and promote ligand discovery and characterization...
  38. ncbi Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in mice
    Ruggero Galici
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Ave. S. at Pierce, 417-D Preston Research Building, Nashville, TN 37232-6600, USA
    J Pharmacol Exp Ther 318:173-85. 2006
    ....
  39. ncbi A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Mol Pharmacol 76:356-68. 2009
    ....
  40. ncbi Metabotropic glutamate receptors in the basal ganglia motor circuit
    P Jeffrey Conn
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 417 D Preson Research Building, Nashville, Tennessee 37232 6600, USA
    Nat Rev Neurosci 6:787-98. 2005
    ....
  41. ncbi New therapeutic frontiers for metabotropic glutamate receptors
    Colleen M Niswender
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 452-B Preston Research Building, Nashville, TN 37232-6600, USA
    Curr Top Med Chem 5:847-57. 2005
    ..These studies suggest the exciting possibility that drugs active at mGlu receptors will be useful in treatment of a wide variety of neurological and psychiatric disorders such as Parkinson's disease, anxiety disorders, and schizophrenia...
  42. ncbi A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtype 5 and blocks the effects of multiple allosteric modulators
    Alice L Rodriguez
    Department of Pharmacology and Program in Translational Neuropharmacology, Vanderbilt University Medical Center, 23rd Ave. South at Pierce, 417-D Preston Research Bldg, Nashville, Tennessee 37232-6600, USA
    Mol Pharmacol 68:1793-802. 2005
    ..These novel compounds provide valuable new insight into the pharmacology of allosteric sites on G protein-coupled receptors and provide valuable new tools for determining the effects of allosteric site ligands in native systems...
  43. ncbi Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4)
    Richard Williams
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:4967-70. 2009
    ..The synthesis takes advantage of an iterative parallel synthesis approach to rapidly synthesize and evaluate a number of analogs of VU0155041...
  44. ncbi Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4
    Colleen M Niswender
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Mol Pharmacol 74:1345-58. 2008
    ..These exciting results provide continued support for mGluR4 as a therapeutic target in PD...
  45. ncbi Glutamate receptors as therapeutic targets for Parkinson's disease
    Kari A Johnson
    Department of Pharmacology, Vanderbilt University, Nashville, TN, USA
    CNS Neurol Disord Drug Targets 8:475-91. 2009
    ..These drugs reverse motor deficits in addition to providing protection against neurodegeneration. Glutamate receptors therefore represent exciting targets for the development of novel pharmacological therapies for PD...
  46. ncbi Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:1972-5. 2010
    ..An iterative library synthesis approach delivered a potent (M(1) EC(50)=830 nM) and highly selective M(1) PAM (>30 microM vs M(2)-M(5))...
  47. ncbi Metabotropic glutamate receptors modulate feedback inhibition in a developmentally regulated manner in rat dentate gyrus
    James J Doherty
    Department of Pharmacology, Emory University Medical School, Atlanta, GA 30322, USA
    J Physiol 561:395-401. 2004
    ..These findings indicate that group II mGluRs modulate excitatory drive to interneurones in a developmentally regulated manner and thereby modulate feedback inhibition in the dentate gyrus...
  48. ncbi Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated
    Jennifer E Ayala
    Department of Pharmacology, Program in Translational Neuropharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Neuropharmacology 54:804-14. 2008
    ....
  49. ncbi 3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats
    Andrew S Felts
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:4390-4. 2010
    ..Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples...
  50. ncbi Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273
    Darren W Engers
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    ChemMedChem 4:505-11. 2009
    ..The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties...
  51. ncbi The antipsychotic potential of muscarinic allosteric modulation
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Drug News Perspect 23:229-40. 2010
    ..These data suggest that selective allosteric activation of either M(1) or M(4) has antipsychotic potential through distinct, yet complimentary mechanisms...
  52. ncbi Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)
    Darren W Engers
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:5175-8. 2010
    ..An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu(4) PAM reported to date...
  53. ncbi Metabotropic glutamate receptors mGluR4 and mGluR8 regulate transmission in the lateral olfactory tract-piriform cortex synapse
    Paulianda J Jones
    Department of Pharmacology, Program in Translational Neuropharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Neuropharmacology 55:440-6. 2008
    ..The high potency of L-AP4, combined with the observed effects of DCPG and PHCCC, suggests that both mGluR4 and mGluR8 play a role in the l-AP4-induced inhibition of synaptic transmission at the LOT-PC synapse...
  54. ncbi Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity
    Alice L Rodriguez
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, 2215 Garland Avenue, Nashville, TN 37232 0697, USA
    Mol Pharmacol 78:1105-23. 2010
    ..In addition, these studies provide strong support for the hypothesis that multiple structurally distinct mGluR5 modulators have robust activity in animal models that predict efficacy in the treatment of CNS disorders...
  55. ncbi A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis
    Michael A Benneyworth
    Department of Pharmacology, Vanderbilt University School of Medicine, 8140 MRB III, Nashville, TN 37232, USA
    Mol Pharmacol 72:477-84. 2007
    ....
  56. ncbi Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)
    Darren W Engers
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Med Chem 52:4115-8. 2009
    ..Compounds 9b and 9c showed submicromolar potency at both human and rat mGluR4. In addition, both 9b and 9c were shown to be centrally penetrant in rats using nontoxic vehicles, a major advance for the mGluR4 field...
  57. ncbi A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning
    Jana K Shirey
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6600, USA
    J Neurosci 29:14271-86. 2009
    ....
  58. ncbi Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS
    Ya Zhou
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:6502-6. 2009
    ..This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and further examples of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold...
  59. ncbi Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5
    Andrew S Felts
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:6623-6. 2009
    ..This Letter describes the SAR of this series and the profile of selected compounds in selectivity and radioligand binding assays...
  60. ncbi Discovery of molecular switches that modulate modes of metabotropic glutamate receptor subtype 5 (mGlu5) pharmacology in vitro and in vivo within a series of functionalized, regioisomeric 2- and 5-(phenylethynyl)pyrimidines
    Sameer Sharma
    Department of Chemistry, Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Med Chem 52:4103-6. 2009
    ....
  61. ncbi Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins
    Thomas M Bridges
    Vanderbilt Program in Drug Discovery, Department of Pharmacology and Chemistry, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    J Med Chem 52:3445-8. 2009
    ..Subsequent optimization led to the discovery of VU0238429, which possessed an EC(50) of approximately 1.16 microM at M5 with >30-fold selectivity versus M1 and M3, with no M2 or M4 potentiator activity...
  62. ncbi Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype
    Alice L Rodriguez
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:3209-13. 2009
    ..This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and the first example of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold...
  63. ncbi mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning
    Jennifer E Ayala
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    Neuropsychopharmacology 34:2057-71. 2009
    ..Discovery of small molecules that enhance both LTP and LTD in an activity-appropriate manner shows a unique action on synaptic plasticity that may provide a novel approach for the treatment of impaired cognitive function...
  64. ncbi Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats
    Ashley E Brady
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    J Pharmacol Exp Ther 327:941-53. 2008
    ....
  65. ncbi Differential regulation of metabotropic glutamate receptor 5-mediated phosphoinositide hydrolysis and extracellular signal-regulated kinase responses by protein kinase C in cultured astrocytes
    Richard D Peavy
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA
    J Neurochem 83:110-8. 2002
    ..This differential regulation of mGluR5-mediated responses suggests divergent signaling and regulatory pathways which may be important mechanisms for dynamic integration of signal cascades...
  66. ncbi The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats
    Una C Campbell
    Department of Pharmacology, Merck Research Laboratories, San Diego, CA 92121, USA
    Psychopharmacology (Berl) 175:310-8. 2004
    ..For example, the mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate PCP (phencyclidine)-evoked hyperactivity and PCP-induced disruptions in pre-pulse inhibition (PPI) in rats...
  67. ncbi G protein-coupled receptor kinases regulate metabotropic glutamate receptor 5 function and expression
    Scott D Sorensen
    Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Neuropharmacology 44:699-706. 2003
    ..These studies identify novel roles for GRKs in regulating mGluR5 that may serve to further shape the function of these receptors in neurotransmission...
  68. ncbi Direct and indirect modulation of the N-methyl D-aspartate receptor
    M J Marino
    Emory University Department of Pharmacology, Atlanta, GA 30322, USA
    Curr Drug Targets CNS Neurol Disord 1:1-16. 2002
    ....
  69. ncbi A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5
    Wei Lemaire
    Neuroscience-WP46-300, Merck Research Laboratories, West Point, PA 19486, USA
    Mol Pharmacol 64:731-40. 2003
    ....
  70. ncbi Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment
    Michael J Marino
    Department of Neuroscience, Merck Research Laboratories, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 100:13668-73. 2003
    ..These results are evidence for in vivo behavioral effects of an allosteric potentiator of mGluRs and suggest that potentiation of mGluR4 may be a useful therapeutic approach to the treatment of PD...
  71. ncbi Difference in mGluR5 interaction between positive allosteric modulators from two structural classes
    David L Williams
    Department of Neuroscience-WP, Merck Research Laboratories, West Point, Pennsylvania and Rahway, New Jersey
    Ann N Y Acad Sci 1003:481-4. 2003
  72. ncbi Group III metabotropic glutamate receptor-mediated modulation of the striatopallidal synapse
    Ornella Valenti
    Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania 19486 0004, USA
    J Neurosci 23:7218-26. 2003
    ..Consistent with this, we find that intracerebroventricular injections of L-AP4 produce therapeutic benefit in both acute and chronic rodent models of Parkinson's disease...
  73. ncbi Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo
    Craig W Lindsley
    Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Department of Neuroscience, Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Med Chem 47:5825-8. 2004
    ..Compound 8q demonstrated in vivo proof of concept in an animal behavior model where known antipsychotics are active, supporting the development of new antipsychotics based on the NMDA hypofunction model for schizophrenia...
  74. ncbi A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models
    Gene G Kinney
    Neuroscience-West Point, Merck Research Laboratories, West Point, PA 19486, USA
    J Pharmacol Exp Ther 313:199-206. 2005
    ..These effects are consistent with the hypothesis that allosteric potentiation of mGluR5 may provide a novel approach for development of antipsychotic agents...
  75. ncbi Design, synthesis, and in vivo efficacy of glycine transporter-1 (GlyT1) inhibitors derived from a series of [4-phenyl-1-(propylsulfonyl)piperidin-4-yl]methyl benzamides
    Craig W Lindsley
    Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Merck Research Laboratories, P.O. Box 4, West Point, PA 19486, USA
    ChemMedChem 1:807-11. 2006
  76. ncbi Glutamate-based therapeutic approaches: allosteric modulators of metabotropic glutamate receptors
    Michael J Marino
    Neuroscience Drug Discovery - Movement Disorders, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Curr Opin Pharmacol 6:98-102. 2006
    ....
  77. ncbi NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin
    Sudar Alagarsamy
    Ferring Research Institute, Inc, San Diego, CA, USA
    Neuropharmacology 49:135-45. 2005
    ....
  78. ncbi A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain
    Wei Lemaire
    Neuroscience-WP, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Pharmacol Exp Ther 309:568-77. 2004
    ..These results demonstrate that allosteric potentiation of mGluR5 increases the effect of threshold agonist concentrations in native systems...
  79. ncbi Dissociation of protein kinase-mediated regulation of metabotropic glutamate receptor 7 (mGluR7) interactions with calmodulin and regulation of mGluR7 function
    Scott D Sorensen
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA
    Mol Pharmacol 61:1303-12. 2002
    ..Furthermore, our studies suggest that CaM binding is not required for mGluR7-mediated activation of GIRK current...
  80. ncbi Distinct physiological roles of the Gq-coupled metabotropic glutamate receptors Co-expressed in the same neuronal populations
    Ornella Valenti
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA
    J Cell Physiol 191:125-37. 2002
    ..Interestingly, the group I mGluRs are modulated by a rich variety of regulatory systems, which may explain how these receptors can mediate divergent actions when present in the same cell...
  81. ncbi NMDA-induced phosphorylation and regulation of mGluR5
    Sudar Alagarsamy
    Ferring Research Institute Inc, 3550 General Atomics Court, Building 2, Room 443, San Diego, CA 92121, USA
    Pharmacol Biochem Behav 73:299-306. 2002
    ....
  82. ncbi Dopamine modulates the function of group II and group III metabotropic glutamate receptors in the substantia nigra pars reticulata
    Marion Wittmann
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia
    J Pharmacol Exp Ther 302:433-41. 2002
    ..Thus, in a Parkinsonian state, the loss of nigral DA may add to the overall pathophysiological changes in basal ganglia output...
  83. ncbi D1- and D2-like dopamine receptors regulate signaling properties of group I metabotropic glutamate receptors in the rat globus pallidus
    Olga V Poisik
    Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA
    Eur J Neurosci 26:852-62. 2007
    ....
  84. ncbi Metabotropic glutamate receptors
    D D Schoepp
    Pharmacol Biochem Behav 74:255-6. 2002
  85. ncbi Distinct functional roles of the metabotropic glutamate receptors 1 and 5 in the rat globus pallidus
    Olga V Poisik
    Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322, USA
    J Neurosci 23:122-30. 2003
    ..Together, these data illustrate a novel mechanism by which mGluR1 and mGluR5, members of the same family of G-protein-coupled receptors, can interact to modulate neuronal activity in the rat GP...
  86. ncbi Metabotropic glutamate subtype 5 receptors modulate locomotor activity and sensorimotor gating in rodents
    Gene G Kinney
    Department of Neuroscience, Merck, West Point, PA 19486, USA
    J Pharmacol Exp Ther 306:116-23. 2003
    ....
  87. ncbi Interaction between metabotropic glutamate receptor 7 and alpha tubulin
    Julie A Saugstad
    Robert S Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon, USA
    J Neurochem 80:980-8. 2002
    ....
  88. ncbi Glutamate receptors and Parkinson's disease: opportunities for intervention
    Michael J Marino
    Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania 19486-0004, USA
    Drugs Aging 20:377-97. 2003
    ..In particular, NMDA receptor antagonists that selectively target the NR2B subunit and antagonists of the metabotropic glutamate receptor mGluR5 appear to hold promise and deserve future attention...
  89. ncbi Group III metabotropic glutamate-receptor-mediated modulation of excitatory transmission in rodent substantia nigra pars compacta dopamine neurons
    Ornella Valenti
    Neuroscience Drug Discovery, Movement Disorders, Merck Research Laboratories, West Point, PA 19486, USA
    J Pharmacol Exp Ther 313:1296-304. 2005
    ..Interestingly, in an attempt to employ knockout mice to confirm the role of mGluR4, we discovered an apparent species difference suggesting that in mice, both mGluR4 and mGluR8 modulate excitatory transmission in the SNc...
  90. ncbi Modulation of excitatory transmission onto midbrain dopaminergic neurons of the rat by activation of group III metabotropic glutamate receptors
    Ornella Valenti
    Merck Co. Inc, Neuroscience Department, West Point, Pennsylvania 19486, USA
    Ann N Y Acad Sci 1003:479-80. 2003
  91. ncbi Modulation of inhibitory transmission in the rat globus pallidus by activation of mGluR4
    Michael J Marino
    Neuroscience Department, Merck Research Laboratories, Merck Company Inc, West Point, Pennsylvania 19486, USA
    Ann N Y Acad Sci 1003:435-7. 2003
  92. ncbi The glycine transporter type 1 inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine potentiates NMDA receptor-mediated responses in vivo and produces an antipsychotic profile in rodent behavior
    Gene G Kinney
    Department of Neuroscience, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Neurosci 23:7586-91. 2003
    ....
  93. ncbi Pharmacology and expression analysis of glycine transporter GlyT1 with [3H]-(N-[3-(4'-fluorophenyl)-3-(4'phenylphenoxy)propyl])sarcosine
    Pierre J Mallorga
    Merck and Co. Inc, Department of Neuroscience, West Point, WP26A-3000, P.O. Box 4, West Point, PA 19486, USA
    Neuropharmacology 45:585-93. 2003
    ..Overall, this work shows that [3H]NFPS is a valuable tool in studying GlyT1 expression and pharmacology and that NFPS interacts with GlyT1 at a site different from the transporter translocation and ion binding sites...
  94. ncbi Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in the rat globus pallidus
    Olga Poisik
    Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, NE, Atlanta, GA 30329, USA
    Neuropharmacology 49:57-69. 2005
    ..Therefore, our findings do not only shed light on the functions of group II mGluRs in the GP, they also illustrate the therapeutic potential of mGluR-targeting allosteric modulators in neurological disorders such as Parkinson's disease...
  95. ncbi N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity
    Cyrille Sur
    Department of Neuroscience, Merck and Co Inc, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 100:13674-9. 2003
    ..These observations raise the possibility that N-desmethylclozapine contributes to clozapine's clinical activity in schizophrenics through modulation of both muscarinic and glutamatergic neurotransmission...

Research Grants44

  1. REGULATION OF SIGNALING BY MGLUR5
    P Conn; Fiscal Year: 2005
    ..A combination of molecular, biochemical and electrophysiological techniques will be used to directly test these hypotheses. ..
  2. FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES
    P Jeffrey Conn; Fiscal Year: 2010
    ..Studies are proposed to determine the effects of these novel molecules in brain circuits that may be critically involved in treatment of these brain disorders. ..
  3. mGluR4 Potentiators as a Treatment for Parkinson's Disease
    P Conn; Fiscal Year: 2007
    ..This high throughput screen will provide the basis for future studies aimed at developing allosteric potentiators of mGluR4 that are suitable for clinical testing. ..
  4. FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES
    P Conn; Fiscal Year: 2007
    ..These studies will provide important information as to the impact of allosteric potentiators on mGluR function in different of neuronal circuits. ..
  5. Muscarinic receptor activators as novel antipsychotic agents
    P Conn; Fiscal Year: 2009
    ....
  6. Functional effects of mGluR potentiators in the CNS
    P Conn; Fiscal Year: 2009
    ....
  7. REGULATION OF SIGNALING BY MGLUR5
    P Conn; Fiscal Year: 2009
    ..In addition, these studies will have a major impact on thinking about the utility of allosteric potentiators for multiple other GPCRs where development of direct agonists has been problematic. ..
  8. Functional effects of mGluR potentiators in the CNS
    P Jeffrey Conn; Fiscal Year: 2010
    ....
  9. REGULATION OF SIGNALING BY MGLUR5
    P Jeffrey Conn; Fiscal Year: 2010
    ..In addition, these studies will have a major impact on thinking about the utility of allosteric potentiators for multiple other GPCRs where development of direct agonists has been problematic. ..
  10. Muscarinic receptor activators as novel antipsychotic agents
    P Jeffrey Conn; Fiscal Year: 2010
    ....
  11. METABOTROPIC GLUTAMATE RECEPTORS IN BASAL GANGLIA
    P Conn; Fiscal Year: 2007
    ..Furthermore, we will test the hypothesis that agonists or allosteric potentiators of this receptor can provide palliative relief in rodent models of PD by actions in the GP. ..
  12. FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES
    P Conn; Fiscal Year: 1999
    ..Developing an understanding of the physiological roles of each mGluR subtype will ultimately lead to advances in a number of areas of neurobiology. ..
  13. FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES
    P Conn; Fiscal Year: 1993
    ..These studies, coupled with the electrophysiological experiments, will provide valuable information regarding the roles of specific mGluR subtypes in regulating hippocampal function...
  14. FUNCTIONS OF METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES
    P Conn; Fiscal Year: 2003
    ..abstract_text> ..
  15. Throughput Assay:Allosteric Potentiator of GluR (RMI)
    P Conn; Fiscal Year: 2004
    ..This will provide the characterization needed to allow us to optimize this assay for use in future screens of larger compound libraries. ..