COLLEEN NISWENDER

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. pmc The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease
    Carrie K Jones
    Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University, Nashville, TN 37212, USA
    J Pharmacol Exp Ther 340:404-21. 2012
  2. pmc 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
  3. pmc 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
  4. pmc 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
  5. doi 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
  6. 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
  7. 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
  8. pmc 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
  9. pmc 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
  10. ncbi Recent progress in the development of mGluR4 positive allosteric modulators for the treatment of Parkinson's disease
    Craig W Lindsley
    Vanderbilt Program in Drug Discovery, Department of Pharmacology, Vanderbilt Medical Center, Nashville, TN 37232, USA
    Curr Top Med Chem 9:949-63. 2009

Research Grants

  1. Measurement of GPCR-mediated thallium flux:GIRK (RMI)
    COLLEEN NISWENDER; Fiscal Year: 2005
  2. Assay for HTS of Gi/Go-linked GPCRs: mGluR7 as Prot(RMI)
    COLLEEN NISWENDER; Fiscal Year: 2007
  3. METABOTROPIC GLUTAMATE RECEPTORS IN BASAL GANGLIA
    COLLEEN NISWENDER; Fiscal Year: 2009

Collaborators

  • P Conn
  • Craig Lindsley
  • C David Weaver
  • Marianne Amalric
  • Zixiu Xiang
  • Corey R Hopkins
  • Thomas M Bridges
  • Alice L Rodriguez
  • Tomas de Paulis
  • Huiyong Yin
  • Jurgen Wess
  • F Zheng
  • Richard Williams
  • Darren W Engers
  • Kari A Johnson
  • Carrie K Jones
  • Satyawan Jadhav
  • L Michelle Lewis
  • Jana K Shirey
  • Qingwei Luo
  • Jennifer E Ayala
  • Ashley E Brady
  • Patrick R Gentry
  • Usha N Menon
  • Douglas J Sheffler
  • Joy E Marlo
  • Darren Orton
  • Kamondanai Hemstapat
  • Ryan D Morrison
  • Jacob Bode
  • Jonathan W Dickerson
  • Kimberly Italiano
  • Michael Bubser
  • Analisa D Thompson
  • Nathalie Turle-Lorenzo
  • Anna L Blobaum
  • J Scott Daniels
  • Julie D Bolinger
  • H Alex Brown
  • Tasha Nalywajko
  • Cheryl A Austin
  • NELLIE E BYUN
  • Kwangho Kim
  • Emily L Days
  • Mathew M Mock
  • Alexander S Kane
  • Yun Xiang
  • Michael Baxter Williams
  • Rocio Zamorano
  • Natalia T Nalywajko
  • David Weaver
  • Lyndsey Williams
  • Matthew J Mulder
  • Jessica L Banko
  • J T Brogan
  • Douglas Sheffler
  • J Phillip Kennedy
  • Gilles D Tamagnan
  • Yi Nong
  • Herve Da Costa

Detail Information

Publications22

  1. pmc The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease
    Carrie K Jones
    Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University, Nashville, TN 37212, USA
    J Pharmacol Exp Ther 340:404-21. 2012
    ..The present findings provide exciting support for the potential role of selective mGlu₄ PAMs as a novel approach for the symptomatic treatment of PD and a possible augmentation strategy with either L-DOPA or A2A antagonists...
  2. pmc 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...
  3. pmc 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
    ....
  4. pmc 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...
  5. doi 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...
  6. 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...
  7. 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...
  8. pmc 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...
  9. pmc 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...
  10. ncbi Recent progress in the development of mGluR4 positive allosteric modulators for the treatment of Parkinson's disease
    Craig W Lindsley
    Vanderbilt Program in Drug Discovery, Department of Pharmacology, Vanderbilt Medical Center, Nashville, TN 37232, USA
    Curr Top Med Chem 9:949-63. 2009
    ..This review will focus on the explosion of novel mGluR4 PAMs reported in the past year and the further preclinical validation of mGluR4 activation as a potentially groundbreaking treatment for Parkinson's disease...
  11. pmc 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...
  12. pmc 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
    ....
  13. 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...
  14. pmc 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...
  15. pmc 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...
  16. pmc 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...
  17. pmc 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...
  18. doi 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...
  19. pmc 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...
  20. pmc 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
    ....
  21. pmc 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
  22. ncbi Protein engineering of protein kinase A catalytic subunits results in the acquisition of novel inhibitor sensitivity
    Colleen M Niswender
    Department of Pharmacology, University of Washington, Seattle, Washington 98195 7750, USA
    J Biol Chem 277:28916-22. 2002
    ..Application of this combined genetic and pharmacological approach should allow analysis of the specific roles of PKA isoforms in cell culture and in vivo...

Research Grants3

  1. Measurement of GPCR-mediated thallium flux:GIRK (RMI)
    COLLEEN NISWENDER; Fiscal Year: 2005
    ..Identified compounds will provide new pharmacological tools to test the role of the ?2C adrenergic receptor in psychiatric and cardiovascular disorders and the role of GIRK 1/2 channels in the modulation of neuronal excitability. ..
  2. Assay for HTS of Gi/Go-linked GPCRs: mGluR7 as Prot(RMI)
    COLLEEN NISWENDER; Fiscal Year: 2007
    ..abstract_text> ..
  3. METABOTROPIC GLUTAMATE RECEPTORS IN BASAL GANGLIA
    COLLEEN NISWENDER; Fiscal Year: 2009
    ..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. ..