CURRICULUM VITAE

Colleen M. Niswender, Ph.D.

Department of Pharmacology

Vanderbilt University Medical Center

23rd Avenue South at Pierce

1215C MRB IV

Nashville, TN 37232-6600

Phone:  615-343-4303

Fax:  (615) 936-6833

E-mail: colleen.niswender@vanderbilt.edu

EDUCATION

1986-1987          Undergraduate, University of Akron, Akron, Ohio

1987-1991          Undergraduate, University of Toledo, Toledo, Ohio

1991                   B.S., Pharmacy with Honors in Pharmacology, University of Toledo,                             Toledo, Ohio

1991-1996          Graduate Student, Pharmacology, Vanderbilt University

1996                   Ph.D., Pharmacology, Vanderbilt University

PROFESSIONAL TRAINING AND EXPERIENCE

1996-1998          Postdoctoral Fellow, Pharmacology, Vanderbilt University

1998-2003          Senior Fellow, Pharmacology, University of Washington

2003-2004          Acting Instructor, Pharmacology, University of Washington

2004-2009          Research Assistant Professor, Pharmacology, Vanderbilt                                             University, Director, Molecular Pharmacology, Vanderbilt Program                               in Drug Discovery

2009-2017          Research Associate Professor, Pharmacology, Vanderbilt                                            University, Director, Molecular Pharmacology, Vanderbilt Center for                             Neuroscience Drug Discovery

2017-present      Research Professor, Pharmacology, Vanderbilt                                                             University, Director, Molecular Pharmacology, Vanderbilt Center for                             Neuroscience Drug Discovery

AWARDS AND HONORS

1991                   Valedictorian, College of Pharmacy

1991                   Phi Kappa Phi Graduate Fellowship

1991                   AAPS-AFPE Gateway Scholarship

1991                   The Merck-Sharp and Dohme Award in Medicinal Chemistry

1991                   The Upjohn Award in Pharmacology

1991                   The SmithKline Beechem Award in Clinical Pharmacy

1993                   First Place, Vanderbilt University Graduate Student Research Day

1994                   First Place, Vanderbilt University Graduate Student Research Day

1995                   Grass Foundation Fellowship to attend “Neurobiology of Human                                 Neurological Disease: Mechanisms of Neurodegeneration”, Cold                                 Spring Harbor Laboratory

2000                   Travel award for abstract submitted to “Obesity and the Regulation                              of Energy Homeostasis”, Keystone Symposium, Taos, NM

PROFESSIONAL MEMBERSHIPS

1991-present      Phi Kappa Phi

2006-present      Society for Neuroscience

2007-present      American Society for Pharmacology and Experimental                                                 Therapeutics

RESEARCH SUPPORT-CURRENT (as of 1/18/2018)

1R01 MH108498-01 (Niswender C/Lindsley C)  12/10/2015-11/30/2018                 NIMH                                                                     $1,498,134, Total Project

Development of an mGlu_2/4 heterodimer-selective allosteric modulator. We propose that heterodimerization may underlie a divergence in in vivo pharmacological profiles that we have observed with various mGlu₄ positive allosteric modulators that either do or do not potentiate the activity of mGlu_2/4 heterodimers. We will chemically optimize small molecules with selectivity for mGlu_2/4 heteromers over mGlu₂ or mGlu₄ homomeric receptors.

1R01MH110389-01 (Niswender C/Lindsley C)     07/01/2016-06/30/209                   NIMH                                                                      $1,714,670 Total Project

Optimization of a Metabotropic Glutamate Receptor 7 Positive Allosteric Modulator. We propose to perform a chemical optimization campaign to develop mGlu₇ PAMs with enhanced specificity and pharmacokinetic properties and to use deficits in Mecp2-deficient mice to profile native tissue and in vivo activity of optimized compounds, with the goal of developing a highly selective mGlu₇ PAM to support continued exploration of the biology and therapeutic potential of this important receptor.

PR160102 (Niswender C)                                   08/01/2017-07/31/2020                  Department of Defense                                      $1,875,949, Total Project  

The Role of Metabotropic Glutamate Receptor 7 in the Etiology and Treatment of Rett Syndrome. This grant will examine the role of mGlu₇ in Rett syndrome by profiling mGlu₇ knockout mice, crossing mice with various mGlu₇ expression levels with Mecp2-deficient animals, and developing new mGlu₇ negative allosteric modulator probes.

 3503  (Niswender, C)                                           04/01/2017-03/31/2019                 Rettsyndrome.org                                               $150,000, Total Project     

Exploration of Metabotropic Glutamate Receptor 3 as a Target for MeCP2-Related Disorders. This grant proposes to determine if mGlu₃ is a new target that can be modulated with small molecules for therapeutic benefit in models of MeCP2-related disorders.

 3511 (Niswender, C)                                            04/01/2018-03/31/2020                 Rettsyndrome.org                                               $150,000, Total Project     

Tailoring Gene Replacement Therapy for MECP2-Related Disorders. This grant proposes to determine if mGlu₃ is a new target that can be modulated with small molecules for therapeutic benefit in models of MeCP2-related disorders.

 

RESEARCH SUPPORT-COMPLETED (as of 1/18/2018)

Predoctoral/Postdoctoral Awards

1994-1996                  Pharmaceutical Research and Manufacturers of America                                             Foundation, Predoctoral Award in Pharmacology

1997-1998                 Pharmaceutical Research and Manufacturers of America                                             Foundation  Postdoctoral Award in Pharmacology

1999-2000                  Fellow, Neurobiology and Behavior Training Grant, University                                     of  Washington

2000-2003                  Fellow, National Service Research Award, NIDDK

03/1/03-02/28/04         University of Washington Diabetes and Endocrinology                                                  Research Center, Pilot and Feasibility Award

 

1 R03 MH076398-01 (Niswender, C)                                  08/1/05-07/31/06       NIH/NIMH                                                                            $3,000 plus HTS

Measurement of GPCR-Mediated Thallium Flux through GIRK.  This grant provided access to high-throughput screening (HTS) through the Molecular Libraries Screening Center Network to search for modulators of the alpha 2C receptor.

1R21NS053536-01/1R21NS053536-01S1 (Niswender, C) 09/30/05-02/28/08          NIH/NIMH                                                                             $125,000 plus $25,000                                                                                                  Supplement 

A Direct Assay for HTS of Gi/o-linked GPCRs: mGluR7 as the Prototype. This grant funded assay development to design an HTS-compatible assay to search for novel modulators of metabotropic glutamate receptor 7.

1X01 MH077607-01 (Niswender, C)                                    02/01/06-01/31/07  NIH/NIMH                                                                              HTS funding

Discovery of novel allosteric agonists of the M4 muscarinic receptor.                  This grant provided access to high-throughput screening (HTS) through the Molecular Libraries Screening Center Network to search for modulators of the M4 muscarinic receptor.

1R01 (Niswender, C)                                                             02/01/04-11/30/09    NIH/NINDS                                                                             $1,165,000              

Metabotropic Glutamate Receptors in Basal Ganglia.  This grant examined the role of group III metabotropic glutamate receptors in modulating circuitry in the basal ganglia as novel treatments for Parkinson’s disease and other movement disorders. Grant transferred from P. Jeffrey Conn in final year of funding.

LEAPS Award (Conn, PJ)                                                   01/01/07-10/30/11  Michael J. Fox Foundation                                                 $3,609,000 

Discovery of novel allosteric modulators of mGluR4 for treatment of Parkinson’s disease.  This grant was a lead optimization program to develop an mGlu4 positive allosteric modulator for the treatment of Parkinson’s disease. Role: Biology Project Team Leader

Basic Research Award (Niswender, CM)                          01/01/12-12/31/13            International Rett Syndrome Foundation                         $100,000                     

Metabotropic Glutamate Receptor 7: a Novel Therapeutic Candidate for Rett Syndrome. This grant examined the regulation of mGlu₇ levels in the context of MeCP2 loss and provided the basis for new grants to develop novel allosteric modulators for MeCP2-based disorders.

R21 NS078262 (Niswender, CM)                                        04/01/12-03/13/14            NIH/NINDS                                     $420,809, Total Project                                          Metabotropic Glutamate Receptors in the Basal Ganglia. The goals of this grant were to test the hypothesis that metabotropic glutamate receptor 8 is a novel target in Parkinson’s disease. The grant involved a combination of molecular pharmacology, electrophysiology, and in vivo behavioral profiling.

1UH2 NS099066-01 (Niswender, CM)                                09/01/2016-09/29/2021    NIH /NINDS                                    $124,768, Total Project                                  Development of VU0652957 for the treatment of Parkinson’s disease (PD). We propose to utilize the Blueprint Neurotherapeutics Network (BPN) to advance VU0652957 through Investigational New Drug (IND)-enabling studies in preparation for clinical studies in PD patients. This is a development grant to advance an mGlu₄ positive allosteric modulator into clinical development for Parkinson’s disease. Project ended due to lack of exposure required for efficacy in a nonhuman primate model of Parkinson’s disease.

5R21 MH102548-02 (Niswender, CM)        08/01/2014-07/31/2017       

NIMH                                                             $431,476, Total Project

Metabotropic Glutamate Receptor Regulation in MeCP2-Related Disorders.

Based on dramatic decreases in mGlu₇ levels seen in mice that model Rett syndrome, we propose to test the hypothesis that mGlu₇ levels are conversely increased in an MECP2 Duplication mouse model, further substantiating a role for MeCP2 in mGlu₇ gene regulation. Additionally, we will test the hypotheses that modulation of mGlu₇ activity using pharmacological tools will normalize synaptic plasticity and behavioral deficits in mice under- and overexpressing MeCP2.

 

8766 (Niswender, C)                                           03/01/2014-08/28/2017                    Autism Speaks                                                   $449,996, Total Project

Temporal Divergence of Hypoconnectivity and Excitotoxicity in Rett Syndrome. The goals of these studies are to build upon our preliminary data showing that mGlu₅ PAMs reduce symptom severity and phenotypes in RS mice when administered in advanced disease states. We will also assess the liability for PAMs to elicit adverse consequences when administered early in disease due to temporal changes in glutamatergic transmission. Furthermore, we will determine whether mGlu₅ NAMs can temper excitotoxicity and prevent synapse loss when administered to young RS mice, thereby reducing the impact of developmental regression on RS phenotypes.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

INTRAMURAL AND EXTRAMURAL ACTIVITIES

 

2006

 

–Grant reviewer, Melanoma Research Foundation

-Manuscript reviewer, Journal of Neurochemistry

-Paper discussion leader for Interdisciplinary Graduate Program Core Course. Kim et al., 2001, JBC. The role of phosphorylation in DI dopamine receptor desensitization.

 

2007

 

-Manuscript reviewer, Molecular Pharmacology

-Lecturer in Neuroscience 345 Course.  Neuromodulation and metabotropic glutamate receptors.

-Paper discussion leader in Neuroscience 345 Course. Sansig et al., 2001, J. Neuroscience. Increased seizure susceptibility in mice lacking metabotropic glutamate receptor 7.

-Paper discussion leader for Interdisciplinary Graduate Program Core Course. Ross et al., 1978 JBC. Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme.

 

2008

 

-Manuscript reviewer, Neuropharmacology

-Paper discussion leader for Interdisciplinary Graduate Program Core Course. Kim et al., 2001, JBC. The role of phosphorylation in DI dopamine receptor desensitization.

-Lecturer in Neuroscience 345 Course. Neuromodulation and metabotropic glutamate receptors.

-Paper discussion leader in Neuroscience 345 Course. Volk et al., 2007, J. Neuroscience. Multiple Gq coupled receptors converge on a common protein synthesis-dependent long term-depression that is affected in fragile X mental retardation.

 

2009

 

Grant reviewer, Michael J. Fox Foundation

Manuscript reviewer, Molecular Pharmacology

Manuscript reviewer, ACS Chemical Neuroscience

Manuscript reviewer, Journal of Neuroscience

Manuscript reviewer, J Pharmacol Exp Therapeutics

Manuscript reviewer, British Journal of Pharmacology

 

2010

Manuscript reviewer, British Journal of Pharmacology

Manuscript reviewer, Molecular Pharmacology

Manuscript reviewer, Neuropharmacology

Manuscript reviewer, Neuroscience

 

2011

Manuscript reviewer, Journal of Biological Chemistry

Manuscript reviewer, The International Journal of Neuropsychopharmacology

Manuscript reviewer, Nature Protocols

Manuscript reviewer, Proceedings of the National Academy of Sciences

 

2012

Grant reviewer, Multiple Sclerosis Fast Forward Foundation

Manuscript reviewer, Expert Opinion on Drug Discovery

Manuscript reviewer, Neuropharmacology

Manuscript reviewer, Pharmacology, Biochemistry, and Behavior

Manuscript reviewer, Molecular Pharmacology

Manuscript reviewer, ACS Chemical Neuroscience

Guest lecturer, Drug Discovery Course. “mGlu₄ positive allosteric modulators for the treatment of CNS disorders”. Vanderbilt University, October 17, 2012.

 

2013

-Manuscript reviewer, Journal of Neurochemistry

-Manuscript reviewer, Neuropharmacology

-Grant reviewer, Michael J. Fox Foundation

-Grant reviewer, Pilot and Feasibility Awards program, Vanderbilt University for Obesity and Metabolism

-Grant reviewer, NIH EUREKA program

-Special Guest Editor, Neuropharmacology, “The Synaptic Basis of Neurodegeneration”

-Manuscript reviewer, Journal of Neurochemistry

-Guest lecturer, Neuroscience 235 Course. “Drug Discovery in Academia: mGlu4 positive allosteric modulators for the treatment of CNS disorders”. Vanderbilt University, March 14, 2013.

-Guest lecturer, Drug Discovery Course. “mGlu₄ positive allosteric modulators for the treatment of CNS disorders”. Vanderbilt University, November 6, 2013.

-Co-organizer, Academic Drug Discovery Conference, Nashville TN, October 9-11, 2013.

 

2014

-Manuscript reviewer, Molecular Pharmacology

-Manuscript reviewer, Neuropharmacology

-Manuscript reviewer, Journal of Pharmacology and Experimental Therapeutics

-Grant reviewer, Trailblazer Award, Autism Speaks

-Guest lecturer, Neuroscience 235 Course. “Drug Discovery in Academia: mGlu4 positive allosteric modulators for the treatment of CNS disorders”. Vanderbilt University, March 11, 2014.

-Grant reviewer, IWT

-Grant reviews, Meixner Postdoctoral Fellowship Program, Autism Speaks

-Guest lecturer, Drug Discovery Course. “mGlu₄ positive allosteric modulators for the treatment of CNS disorders”. Vanderbilt University, October, 2014.

 

2015

-Manuscript reviewer, Neuropharmacology

– Guest lecturer, Neuroscience 235 Course. “Drug Discovery in Academia: mGlu4 positive allosteric modulators for the treatment of CNS disorders”. Vanderbilt University, February 24, 2015.

-Grant reviewer, Meixner Postdoctoral Fellowship Program, Autism Speaks

-Guest lecturer, Drug Discovery Course. “mGlu₄ positive allosteric modulators for the treatment of CNS disorders”. Vanderbilt University, October, 2015.

 

2016

-Manuscript reviewer, Neuropharmacology

-Manuscript reviewer, Frontiers in Neural Circuits

– Guest lecturer, Neuroscience 235 Course. “Drug Discovery in Academia: mGlu4 positive allosteric modulators for the treatment of CNS disorders”. Vanderbilt University, February 24, 2015.

-Guest lecturer, Modern Drug Discovery, “mGlu4 positive allosteric modulators for the

-Grant reviewer, Meixner Postdoctoral Fellowship Program, Autism Speaks

-Member, VICTR “Drug Repurposing Think Tank”

 

2017

-Manuscript reviewer, Neuropharmacology

-Introduction to the Vanderbilt Center for Neuroscience Drug Discovery: Case Study in Rett Syndrome, MSTP Second Look Day, Vanderbilt University, April 7, 2017.

-Co-chair of Autism Spectrum Disorders Speaking Session, 9^th International Meeting on Metabotropic Glutamate Receptors

 

 

STUDENTS/POSTDOCS DIRECTLY SUPERVISED/THESIS COMMITTEES

 

Caroline Kim                   VUMC Emphasis Program for Medical Students, 2007-2008. ‘Investigation of type III metabotropic glutamate receptor potentiators using a novel HTS assay using thallium flux through GIRK channels”. Current position, General Surgeon at Houston Methodist, San Jacinto.

 

Alexander Kane             Vanderbilt University undergraduate. “The in vivo characterization of TBPB, a novel allosteric agonist of M1 muscarinic receptors: Implications for the role of M1 muscarinic receptors in treatment of schizophrenia”. Honors thesis, May, 2008.

 

Shen Yin                         Vanderbilt University pharmacology graduate student. Co-mentor, graduated September, 2013. “Allosteric modulation of metabotropic glutamate receptors”. Current position, Associate Clinical Scientist, Genentech.

 

Olivia Veatch                  Vanderbilt University genetics graduate student. Thesis committee member, graduated August, 2013. “Identifying biological pathways implicated in defined subgroups of phenotypic expression for autism spectrum disorders.” Current position, Research Instructor in Neurology, Vanderbilt Kennedy Center.

 

Frank Byers                    Vanderbilt University Masters in Laboratory Investigation student, thesis committee, graduated May 2014.

 

Rebecca Klar Senter     Vanderbilt University pharmacology graduate student, Co-mentor. Awarded Weatherstone predoctoral fellowship from Autism Speaks 7/1/2014, graduation 7/14/2015. Current position, Scientist, Flexion Therapeutics.

 

Rachel Crouch               Vanderbilt University pharmacology graduate student, co-chair of thesis committee. Graduation 11/2016. Current position, Postdoctoral fellow, VCNDD.

 

Thomas Utley                 Vanderbilt University pharmacology postdoc. Current position, Licensing Agent, Vanderbilt Technology Transfer office.

 

Julie Roper-Field           Vanderbilt University pharmacology postdoc. Current position, Project Manager, VICTR and CTSA Consortium Coordinating Center, Vanderbilt University Medical Center.

 

Nidhi Jalan-Sakrikar     Vanderbilt University pharmacology postdoc (2012-2014), Current position, postdoctoral fellow at Mayo Clinic.

 

Rocco Gogliotti               Vanderbilt University pharmacology postdoc, joined lab in 2012, awarded postdoctoral fellowship from International Rett Syndrome Foundation, 2014. Awarded BBRF fellowship in 2016 (current).

 

Nicole Fisher                  Vanderbilt University Interdisciplinary Graduate Student, joined lab Spring of 2015, awarded Pharmacology Training grant slot, 2015 (current).

 

Branden Stansley          Vanderbilt University Pharmacology Postdoctoral Fellow, joined lab Spring of 2015, awarded T32 postdoctoral training award and an F32 NRSA, June 2016 (current).

 

Sheryl Vermudez              Vanderbilt University Interdisciplinary Graduate Student, joined lab Spring of 2017 (current).

 

Annah Moore                 Vanderbilt University Interdisciplinary Graduate Student, joined Sweatt Lab in Spring of 2017, co-mentor (current).

 

Christian Marks                 Vanderbilt University Molecular Physiology and Biophysics Graduate Student, thesis committee (current).

 

Sean Moran                       Vanderbilt Neuroscience Graduate Student, thesis committee (current).

 

Nick Harris                        Vanderbilt University Molecular Physiology and Biophysics MD/PhD Student, thesis committee (current).

 

Mabel Seto                        Vanderbilt University Interdisciplinary Graduate Student, thesis committee (current).

 

Christopher Hofmann   Vanderbilt University Interdisciplinary Graduate Student, thesis committee (current).

 

 

Rotation students

 

Yerai Oliveres (2004), Alex Nakenoff (2009), Michael Nedelcovych (2009), Shen Yin (2009) Sahana Naganhushan Kalburgi (2014), Aparna Shekar (2014), Nicole Fisher (2015), Francis Prael (2015), Nathan Winters (2017), Annah Moore (2017), Sheryl Vermudez (2017), Sarah Naguib (2017)

 

 

PRESENTATIONS

 

1998

 

-Identification and Functional Characterization of Edited Human Serotonin 2c Receptor Isoforms. 4^th IUPHAR Satellite Meeting on Serotonin. October 1998.

 

2006

 

-High Throughput Screening and Medicinal Chemistry at Vanderbilt in Support of Drug Discovery for Muscarinic Receptor Ligands. Vanderbilt Institute for Chemical Biology Retreat.

 

-Allosteric modulation of metabotropic glutamate receptor 5, M1, and M4 muscarinic receptors: potential therapeutic directions for schizophrenia. 27^th Annual Meeting of the Southeastern Pharmacology Society. November 2006.

 

 

2007

 

-High Throughput Screening and Medicinal Chemistry at Vanderbilt: The search for Allosteric Ligands of the M1 and M4 Muscarinic Receptors. HTS Users Group Meeting, Vanderbilt University. March, 2007

 

2008

 

-Allosteric modulation of mGluR4 as a novel therapeutic direction for the treatment of Parkinson’s disease. American Society for Biochemistry and Molecular Biology, Experimental Biology, San Diego, CA. April, 2008.

 

-Allosteric modulation of GCPRs as a novel therapeutic direction for the treatment of CNS disorders. American Society of Pharmacology and Experimental Therapeutics, Experimental Biology, San Diego, CA, April. 2008.

 

-Allosteric modulation of mGluR4 as a novel therapeutic direction for the treatment of Parkinson’s disease. Keystone Symposia; G Protein Coupled Receptors: New Insights in Functional Regulation and Clinical Application, Killarney, Ireland. May, 2008.

 

-Allosteric modulation of mGluR4: a novel therapeutic direction for the treatment of Parkinson’s disease.  6^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy. September, 2008.

 

2009

 

-The development of positive allosteric modulators of mGluR4 for the treatment of Parkinson’s disease. WFN World Congress on Parkinson’s Disease and Related Disorders. Miami, FL. December, 2009.

2010

 

-The development of positive allosteric modulators of mGluR4 for the treatment of Parkinson’s disease—Parkinson’s Disease Case Study. 4th Annual Drug Discovery for Neurodegeneration Conference. Houston, TX. February, 2010.

 

-HTS results from academia: discovery of allosteric modulators of mGluR4 and 5. Metabotropic Glutamate Receptors: Translation from Discovery to Clinical Trials. The New York Academy of Sciences. New York, NY. February, 2010.

 

-Functionally selective and context dependent pharmacology of GPCR allosteric modulators.  Pharmacology drive assays for GPCRs and ion channels. Ninth Annual World Pharmaceutical Congress. Philadelphia, PA, June, 2010.

 

-Novel ion channel-based assays: detecting and characterizing 7TM receptor modulators. Pharmacology drive assays for GPCRs and ion channels. Ninth Annual World Pharmaceutical Congress. Philadelphia, PA, June, 2010.

 

-The Development of Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4. Allosteric Modulator Drug Discovery Congress, San Diego, CA, November, 2010.

 

2011

 

-mGlu4 receptor positive allosteric modulator development for the treatment of CNS disorders. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Italy. October, 2011.

 

 

2012

 

-mGlu4 positive allosteric modulators for the treatment of CNS disorders. 45^th Annual Winter Conference on Brain Research. Snowbird, Utah, January.

 

2013

 

-mGlu4 positive allosteric modulators for the treatment of CNS disorders. Guest presentation to Vanderbilt Parkinson’s Disease Advisory Board, Vanderbilt University, April 19, 2013.

 

-Metabotropic glutamate receptor 7: a novel therapeutic target for MeCP2-related disorders. Vanderbilt University Rett Syndrome Symposium, October 16, 2013.

 

2014

-Metabotropic glutamate receptor potentiation as a therapeutic direction in Rett syndrome. Invited talk, International Rett Syndrome Foundation meeting, June 25, 2014.

 

-Metabotropic glutamate receptor 7 (mGlu₇): a novel target for the treatment of Rett syndrome. Invited talk, 8^th International Meeting on Metabotropic Glutamate Receptors, October 2, 2014.

 

-Metabotropic glutamate receptor 7 (mGlu₇): a novel target for the treatment of Rett syndrome. Invited talk, Multimodal Interventions in IDD from Drug Discovery to Clinical Trials, Vanderbilt Kennedy Center, October 22, 2014.

 

2015

 

-Metabotropic glutamate receptor 7: a new therapeutic target for both Rett and MECP2 Duplication syndromes. Invited talk, MECP2 Duplication Conference, Houston TX, Sept 2015.

 

2016

 

-Metabotropic Glutamate Receptor 4 Positive Allosteric Modulators for Parkinson’s Disease: Impact of Receptor Heterodimerization. CNS Diseases World Summit. Boston, MA, Sept 12, 2016.

 

2017

 

-Therapeutic Potential of mGlu7 in Neurodevelopmental Disorders. Invited Speaker, 9^th International Meeting on Metabotropic Glutamate receptors. Taormina, Italy, October 2017.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ISSUED PATENTS

 

1. Benzamide mGluR5 Positive Allosteric Modulators and Methods of Making and Using Same. Patent 8,853,392. Filed 6/3/2008. Issued patent, USA.

 

1. Benzamide mGluR5 Positive Allosteric Modulators and Methods of Making and Using Same. Patent 5622568. Filed 12/2/2009. Issued patent, Japan.

 

1. Substituted Dioxopiperidines and Dioxopyrrolidines as mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent 8,759,377. Filed 11/23/2010. Issued patent, USA.

 

1. Alkyl-3-((2-Amidoethyl)Amino)-8-Azabicyclo[3.2.1]Octane-8-Carboxylate Analogs as M1 Allosteric Agonists and Methods of Making and Using Same. Patent 8,697,691. Filed 12/21/2010. Issued patent, USA.

 

1. Substituted 1,1,3,1-Tetraoxidobenzo{D} {1,3,2}Dithiazoles as mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent 8,658,650. Filed 1/28/2011. Issued patent, USA.

 

1. Pyrazolopyridine, Pyrazolopyrazine, Pyrazolopyrimidine, Pyrazolothiophene and Pyrazolothiazole Compounds as mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent zl 201180017221.4. Filed 2/11/2011. Issued patent, China.

 

1. Pyrazolopyridine, Pyrazolopyrazine, Pyrazolopyrimidine, Pyrazolothiophene and Pyrazolothiazole Compounds as mGluR4 Allosteric Potentiators, Compounds, and Methods of Treating Neurological Dysfunction. Patent 2012/06416. Filed 2/11/2011. Issued patent, South Africa.

 

1. Pyrazolopyridine, Pyrazolopyrazine, Pyrazolopyrimidine, Pyrazolothiophene and Pyrazolothiazole Compounds as mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent 9,163,015. Filed 2/11/2011. Issued patent, USA.

 

1. Pyrazolopyridine, Pyrazolopyrazine, Pyrazolopyrimidine, Pyrazolothiophene and Pyrazolothiazole Compounds as mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent 2011215638. Filed 2/11/2011. Issued patent, Australia.

 

1. Pyrazolopyridine, Pyrazolopyrazine, Pyrazolothiophene and Pyrazolothiazole Compounds as mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent 9,108,963. Filed 8/13/2012. Issued patent, USA.

 

1. mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Filed 4/23/2012. Patent 9,180,192. Issued patent, USA.

 

1. mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent 8,779,157. Filed 6/12/2012. Issued patent, USA.

 

1. Aryl and Heteroaryl Sulfones as mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent 8,912,336. Filed 6/12/2012. Issued patent, USA.

 

1. Benzisoxazoles and Azabenzisoxazaoles as mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction, Patent 8,916,584, Filed 8/13/2012. Issued patent, USA.

 

1. Heterocyclic Sulfone mGluR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction. Patent 9,192,603, Filed 11/13/2012. Issued patent, USA.

 

ABSTRACTS

 

1. Burns, CM, Obermiller PS, Emeson RB.  RNA editing of AMPA receptor subunit (GluR-B) mRNA. , Society for Neuroscience Abstracts, 1993.

 

2. Burns CM, Rueter SM, Emeson RB.  Molecular mechanisms mediating the editing of glutamate receptor (GluR-B) RNA transcripts.  Albany Conference, RNA Editing, 1994.

 

3. Rueter, SM, Burns CM and Emeson RB. In vitro editing of glutamate receptor (GluR-B) RNA transcripts. RNA Processing: Cold Spring Harbor Laboratory, 1995.

 

4. Burns CM, Chu H, Rueter SM, Sanders-Bush E, Emeson RB. Identification and characterization of RNA editing within the serotonin 2C receptor. Society for Neuroscience Abstracts, 1996.

 

5. Chu H, Burns C, Canton H, Emeson RB, Sanders-Bush E. Functional characterization of rat serotonin 5-HT_2C receptor editing isoforms. Society for Neuroscience Abstracts, 1996.

 

6. Rueter SM, Burns CM, Emeson RB. Characterization of AMPA receptor subunit (GluR-B) RNA editing in rat brain nuclear extracts. Society for Neuroscience Abstracts, 1996.

 

7. Burns CM, Chu H, Rueter SM, Sanders-Bush E, Emeson RB. RNA editing of transcripts encoding the serotonin 2C receptor. EMBO workshop on RNA Editing, 1996.

 

8. Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB. RNA editing of serotonin 2C receptor transcripts. RNA Society Meeting, 1997.

 

9. Niswender CM, Copeland S, Emeson RB and Sanders-Bush E. Identification and Functional Characterization of Edited Human Serotonin 2c Receptor Isoforms. 4^th IUPHAR Satellite Meeting on Serotonin, 1998.

 

10. Niswender CM, Copeland SC, Dilley G., Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E.  RNA editing of human serotonin 2C receptor transcripts. Society for Neuroscience Abstracts,

 

11. Berg KA, Cropper JD, Niswender CM, Sanders-Bush E, Emeson RB Clarke WP. Activation of PLC and PLA₂ by h5-HT_2C receptor RNA-edited isoforms. Society for Neuroscience Abstracts,

 

12. Niswender CM, McKnight GS. Cre recombinase-mediated expression of a constitutively active form of protein kinase A. Keystone Conference, Obesity and the Regulation of Energy Homeostasis, Taos, NM, 2001.

 

13. Willis BS, Niswender CM, McKnight GS. Cre recombinase-mediated expression of dominant-negative and constitutively active protein kinase A subunits. Society for Neuroscience Abstracts, 2001.

 

14. Niswender CM, Willis BS, Sweet IR, Wallen A, Thompson B, Wu C, Lange AJ, McKnight GS. Expression of a constitutively active PKA holoenzyme in the liver results in glucose intolerance and impaired glucose-stimulated insulin secretion in mice. Keystone Conference, Toward Understanding Islet Biology, Keystone, CO, 2003.

 

15. Niswender CM, Myers KA, Banko JL, Rodriguez AL, Edl J, Zhang Y, Shirey JK, Saleh SA, Weaver CD, Conn PJ. Identification of novel allosteric modulators of group III mGluRs: New tools for the study of synaptic transmission. 5^th Meeting on Metabotropic Glutamate Receptors, Taormina, Italy, 2005.

 

16. Edl J, Rodriguez AL, Tamagnan G, Alagille D, Johnson RL, Niswender C, Myers K, Conn PJ. Characterization of structural analogs of a Group III mGluR agonist and mGluR4/5 allosteric modulators. Society for Neuroscience Abstracts, 2005.

 

17. Myers KA, Niswender CM, Williams R, Edl J, Saleh S, Jones CK, Weaver CD, Orton D, Conn PJ. Characterization of novel allosteric antagonists of metabotropic glutamate receptor subtype 7. Society for Neuroscience Abstracts, 2006.

 

18. Brady AE, Shirey JK, Rodriguez AL, Niswender CM, Weaver CD, Conn, PJ. A high throughput functional screen for the identification of selective allosteric ligands of the M1 mAChR. Society for Neuroscience Abstracts, 2006.

 

19. Edl J, Banko JL, Myers KA, Niswender CM, Conn PJ. Developmental differences in group III mGluR regulation of synaptic transmission in area CAI of the rat hippocampus. Society for Neuroscience Abstracts, 2006.

 

20. Niswender CM, Myers KA, Williams R, Ayala J, Luo Q, Saleh S, Jones CK, Weaver CD, Orton D, Conn PJ. Permissive antagonism induced by novel allosteric antagonists of metabotropic glutamate receptor 7. American College of Neuropsychopharmacology Abstracts, 2006.

 

21. Conn PJ, Weaver CD, Niswender C, Brady A, Shirey J, Edl J. Discovery and characterization of novel allosteric modulators of GPCRs. American College of Neuropsychopharmacology Abstracts, 2006.

 

22. Niswender CM, Jones CK, Weaver CD, Rodriguez AL, Chen Y, Shirey JK, Brady AE, Marlo JE, Luo Q, Xianzhang M, Williams L, Hammond AS, Myers KA, Orton D, Williams R, Days EL, Nalywajko NT, Williams, M, Conn PJ. Allosteric modulation of metabotropic glutamate receptor 5, M1 and M4 muscarinic receptors: potential therapeutic directions for schizophrenia. Southeastern Pharmacology Society Abstracts, 2006.

 

23. Niswender CM, Weaver CD, Lindsley CW, Jones CK, Lewis M, Marlo JE, Shirey JK, Xiang Z, Brady AE, Orton D, Williams R, Rodriguez AL, Yin H, Days EL, Farmer C, Luo Q, Xianzhang M, Myers KA, Ayal JE, Nalywajko NT, Lorsen KA, Williams M, Conn PJ. High Throughput Screening, Medicinal Chemistry, Physiology, and Behavioral Pharmacology at Vanderbilt in Support of Drug Discovery for Targets Involved in CNS Disorders. 8^th Annual Rett Syndrome Symposium, 2007.

 

24. Bridges T, Jones C, Brady A, Marlo J, Rodriguez A, Niswender C, Williams R., Kim K., Sheffler D, Grier M, Weaver D, Conn PJ, Lindsley C. Novel allosteric modulation of the M1 muscarinic receptor: agonists and potentiators for the treatment of Alzheimer’s disease and schizophrenia. ACS-CNS Medicinal Chemistry Conference, 2007.***

 

25. Myers-Johnson KA, Niswender CM, Luo Q, Ayala JE, Rodriguez AL, Marlo JE, Days EL, Nalywajko NT, Lornsen KA, Williams M, Lewis M, Weaver CD, Conn PJ. Discovery, synthesis, and SAR of a series of novel positive allosteric modulators of metabotropic glutamate receptor subtype 4. Society for Neuroscience Abstracts, 2007.

 

26. Shirey, JK, Xiang Z,  Orton D, Brady AE, Johnson KA, Williams R, Ayala JE, Rodriguez AL, Wess J Weaver CD, Niswender CM, Conn PJ. An allosteric potentiator suggests a role for M₄ muscarinic acetylcholine receptor (mAChR) in modulating excitatory hippocampal synaptic transmission. Experimental Biology/American Society of Pharmacology and Therapeutics Abstracts, 2008.***

 

27. Bridges TM, Jones CK, Brady AE, Sheffler DJ, Marlo JE, Niswender CM, Williams R, Williams L, Mulder MJ, Lewis M, Daniels RN, Davis AA, Lah JJ, Levey AI, Weaver CD, Conn PJ, Lindsley CW. Discovery and characterization of novel highly-selective agonists and antagonists of mAChR1: In-vitro and in-vivo profiles relevant to Alzheimer’s disease and schizophrenia. American Society of Pharmacology and Experimental Therapeutics Abstracts, 2008.

 

28. Bridges, TM, Jones CK, Brady AE, Shirey JK, Kennedy JP, Rodriguez AL, Niswender CM, Williams R, Orton D, Gentry PR, Williams L, Mulder M, Weaver CD, Conn PJ, Lindsley CW. Subtype-selective allosteric modulation of the M4 muscarinic acetylcholine receptor. American Chemical Society Meeting Abstracts, 2008.

 

29. Lewis M, Sheffler D, Williams R, Bridges TM, Kennedy PJ, Brogan JT, Mulder MJ, Williams L, Nalywajko NT, Niswender CM, Weaver CD, Conn PJ, Lindsley CW. The discovery and development of a highly selective and centrally active M1 antagonist. American Chemical Society Abstracts, 2008.

 

30. Days, E, Lewis M, Mi D, Luo Q, Dorset D, Bailey S, Farmer C, Niswender C, Conn, PJ, Weaver CD. Discovery of novel allosteric modulators of metabotropic glutamate receptor 8 (mGluR8) using thallium flux modulation in high throughput screening. Society for Biomolecular Screening Abstracts, 2008.***

 

31. Shirey, JK, Xiang Z,  Orton D, Brady AE, Johnson KA, Williams R, Ayala JE, Rodriguez AL, Wess J Weaver CD, Niswender CM, Conn PJ. An allosteric potentiator of M4 muscarinic acetylcholine receptor (mAChR) modulates excitatory hippocampal synaptic transmission. Keystone Conference, G Protein Coupled Receptors: New Insights in Functional Regulation and Clinical Application, Killarney, Ireland, 2008.***

 

32. Conn PJ, Rodriguez AL, Ayala JE, Jones CK, Barrett R, Niswender CM, Weaver CD, Jadhav S, Sheffler DJ, Hammond AS, Williams R, Sharma S, Lindsley CW. Allosteric modulators of metabotropic glutamate receptor 5 as a novel approach for the treatment of CNS disorders. 6^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2008.

 

33. Jones CK, Xiang Z, Jones PJ, Byun NE, Hackler EA, Rodriguez AL, Ayala JE, Niswender CM, Jadhav S, Sheffler DJ, Hammond AS, Barrett R, Thompson AD, Williams R, Gore CJ, Weaver CD, Lindsley CW, Conn PJ. Novel allosteric modulators of metabotropic glutamate receptors 2 and 5 for the treatment of schizophrenia. 6^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2008.

 

34. Niswender CM, Johnson KA, Weaver CD, Jones CK, Luo Q, Rodriguez AL, Marlo JE, de Paulis T, Thompson AD, Days E, Nalywajko T, Austin C, Williams M, Ayala JE, Williams R, Lindsley CW, Conn PJ. Allosteric modulation of mGluR4: a novel therapeutic direction for the treatment of Parkinson’s disease. 6^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2008.

 

35. Niswender CM, Johnson KA, Luo Q, Williams R, Ayala JE, Saleh S, Orton D, Weaver CD, Conn PJ. Permissive antagonism induced by negative allosteric modulators of mGluR7. 6^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2008.

 

36. Niswender CM, Hopkins CR, Jones CK, Thompson AD, Engers S, Williams R, Zhou S, Salovich JM, Cheung YY, Gogliotti R, Gentry P, Johnson KA, Jadhav S, Menon U, Zamorano R, Days EL, Lindsley CW, Weaver CD, Conn PJ. Recent progress in the development of positive allosteric modulators of mGluR4 for the treatment of Parkinson’s disease. Society for Neuroscience Abstracts, 2009.

 

37. Sheffler CJ, Williams R, Bridges TM, Xiang Z, Kane AS, Byun NE, Mock MM, Zheng F, Lewis LM, Jones CK, Niswender CM, Weaver CD, Lindsley CW, Conn PJ. A novel selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonist reduces seizures without impairing hippocampal dependent learning. Society for Neuroscience Abstracts, 2009.

 

38. Niswender CM, Hopkins CR, Jones CK, Thompson AD, Engers S, Williams R, Zhou S, Salovich JM, Cheung YY, Gogliotti R, Gentry P, Johnson KA, Jadhav S, Menon U, Zamorano R, Days EL, Lindsley CW, Weaver CD, Conn PJ. The development of positive allosteric modulators of mGluR4 for the treatment of Parkinson’s disease. International Parkinson’s Disease Congress, 2009.

 

39. Engers DW, Le U, Zhou Y, Jones CK, Thompson AD, Jadhav S, Menon UN, Zamorano R, Daniels JS, Morrison R, Blobaum AL, Weaver CD, Conn PJ, Lindsley CW, Niswender CM, Hopkins CR. Discovery and SAR development of a series of N-(4-acetamido)- and 4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides as Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4:  A Novel Approach for the Treatment of Parkinson’s DiseaseHigh Throughput Chemistry and Chemical Biology Gordon Conference, Les Diablerets, Switzerland, June 2010.

 

40. Gogliotti RD. Hopkins CR, Jones CK, Thompson AS, Engers D, Salovich JM, Cheung Y-Y, Williams R, Gentry PR, Zhou Y, Johnson K, Jadhav S, Menon UN, Zamorano R, Lindslye CW, Conn PJ, Niswender CM. Discovery and SAR development of positive allosteric modulators of metabotropic glutamate receptor 4: a novel approach for the treatment of Parkinson’s Disease. French American Chemical Society, Obernai France, June 2010.

 

41. Utley TJ, Lebois EP, Bridges TM, Melancon BJ, Wood MR, Niswender CM, Lindsley CW, Conn PJ. Identification and characterization of a novel M1 selective muscarinic actylcholine receptor antagonist from an M1 agonist scaffold. Society for Neuroscience Abstracts, 2010.

 

42. Johnson KA, Sheffler CJ, Niswender CM, Xiang Z, Conn PJ. Group II metabotropic glutamate receptor activation induces long-term depression of excitatory transmission in the substantia nigra pars reticulata. Society for Neuroscience Abstracts, 2010.

 

43. Yin S, Zamorano R, Conn PJ, Niswender CM. Histamine: an endogenous allosteric modulator of metabotropic glutamate receptors. Society for Neuroscience Abstracts, 2010.

 

44. Niswender CM, Hopkins CR, Jones CK, Engers D, Thompson AD, Gogliotti RD, Blobaum AE, Jadhav S, Salovich JM, Cheung Y-Y, Morrison RD, Mulder ML, Bolinger J, Dawson ES, Zamorano R, Vinson PN, Bubser M, Brewer KA, Daniels JS, Lindsley CW, Conn PJ. mGluR4 positive allosteric modulator development for the treatment of CNS disorders. Society for Neuroscience Abstracts, 2010.

 

45. Thompson AD, Jones CK, Bubser M, Niswender CM, Hopkins CR, Engers D, Jadhav S, Lindsley CW, Conn PJ. VU0364770, a potent and systemically active positive allosteric modulator of mGluR4, produces robust efficacy in preclinical rodent models of Parkinson’s Disease. Society for Neuroscience Abstracts, 2010.

 

46. Herman EJ, Gregory KJ, Jones CK, Hammond AS, Stauffer SR, Manka J, Weaver C, Niswender CM, Steckler T, Lavreysen H, MacDonald G, Bartolome JM, Mackie C, Lindsley CW, Conn PJ. Optimization of n-aryl piperzaines as selectivity mGluR5 potentiators with efficacy in a rodent model predictive of anti-psychotic activity. Society for Neuroscience Abstracts, 2010.

 

47. Vinson PN, Hammond AS, Rodriguez AL, Townsend SD, Niswender CM, Lindsley CW, Conn PJ. Novel allosteric ligands of mGluR5 conduct unique actions by binding to a distinct site. Society for Neuroscience Abstracts, 2010.

 

48. Noetzel M, Cho HP, Days E, Zhou Y, Rodriguez AL, Steckler T, Lavreysen H, Stauffer SR, Niswender CM, Lindsley CW, Weaver CS, Conn PJ. Receptor expression level influences the effect of allosteric modulators at metabotropic glutamate receptor 5. Society for Neuroscience Abstracts, 2010.

 

49. Niswender CM, Jones CK, Hopkins CR, Thompson AD, Bubser M, Engers DW, Gogliotti RD, Blobaum AL, Salovich JM, Cheung YY, Morrison RD, Dawson ES, Zamorano R, Brewer KA, Daniels JS, Lindsley CW, Conn PJ. mGlu4 receptor positive allosteric modulator development for the treatment of CNS disorders. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

50. Blobaum AL, Morrison RD, Jadhav S, Engers DW, Lindsley SR, Zhou Y, Gogliotti RD, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Hopkins CR, Daniels JS. Drug metabolism and disposition of a novel N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamide series of positive allosteric modulators of metabotropic glutamate receptor 4:identification of ML182 as an orally efficacious mGuR4-PAM. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

51. Conn PJ, Stauffer SR, Zhou S, Manka J, Williams R, Noetzel MJ, Gregory KJ, Vinson P, Niswender CM, Jones CK, Steckler T, MacDonald G, Lindsley CW. Allosteric modulators of metabotropic glutamate receptor 5 for treatment of schizophrenia. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

52. Dawson ES, Smith JA, Niswender CM, Hopkins CR, Gogliotti RD, Stauffer SR, Lindsley CW, Conn PJ. Shape-based virtual screens to identify movel group I and III mGlu receptor allosteric modulator chemotypes. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

53. Engers DW, Le UM, Zhou Y, Thompson AD, Jadhav S, Gogliotti RD, Lindlsey SR, Bolinger JL, Menon UN, Zamorano R, Daniels JS, Morrison RD, Blobaum AL, Jones CK, Weaver CD, Conn PJ, Lindsley CW, Niswender CM, Hopkins CR. Discovery and SAR development of a novel series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides, including ML182, as positive allosteric modulators of metabotropic glutamate receptor 4: a novel approach for the treatment of Parksinon’s disease.  7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

54. Gregory KJ, Dong EN, Reiff SD, Rook JM, Noetzel MJ, Cho HP, Kaufmann KW, Manka JT, Zhou YS, Vinson PN, Stauffer SR, Niswender CM, Lindsley CW, Meiler J, Conn PJ. Application of an operational model of allosterism to investigate the structural determinants of positive allosteric modulator of metabotropic glutamate receptor 5. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

55. Johnson KA, Niswender CM, Conn PJ, Ziang Z. Activation of group II metabotropic glutamate receptors induces long term depression of excitatory synaptic transmissionin the substantia nigra pars reticulate. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

56. Jones CK, Rodriguez AL, Rook JM, Niswender CM, Emmitte KA, Felts AS, Lawson KP, Bates BS, Blobaum AL, Morrison RD, Byers FW, Daniels JS, Carpenter RL, Healy A, Shumway M, Lindsley CW, Conn PJ. Novel mGluR5 NAMs: potential utility to treatment in Fraile X Syndrome and affective disorders. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

57. Noetzel MJ, Gregory KJ, Rook JM, Vinson PN, Cho HP, Stauffer SR, Xiang Z, Daniels JS, Niswender CM, Lindsley CW, Conn PJ. Characterization of novel metabotropic glutamate receptor 5 positive allosteric modulators utilizing in vitro and in vivo studies. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

58. Stauffer SR, S Zhou, Manka J, Rodriguez A, Noetzel MJ, Gregory KJ, Vinson PN, Niswender CM, Dawson E, Jones CK, Lambert R, Thompson AG, Daniels JS, Bridges T, Lavreysen H, Bartolome JM, Mackie C, Steckler T, MacDonald G, Lindsley CW, Conn PJ. Identification and optimization of mGlu5 PAMs which activate the receptor at allosteric sites outside the MPEP site. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

59. Steckler T, Jones CK, Stauffer SR, Bartolome JM, Niswender CM, Lavreysen H, MacDonald G, Mackie C, Vinson P, Daniels JS, Lindsley CW, Conn PJ. mGluR5 positive allosteric modulators: an industrial perspective. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

60. Vinson PN, Rook JM, Stauffer SR, Manka J, Zhou S, Gogi K, Niswender CM, Jones CK, Daniels JS, Bridges T, Lavreysen H, Bartolome JM, Mackie C, Steckler T, MacDonald G, Lindsley CW, Conn PJ. Optimization of mGlu5 positive allosteric modulators for in vivo studies. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.

 

61. Yin S, Zamorano R, Conn PJ, Niswender CM. Histamine: an endogenous modulator of metabotropic glutamate receptors. 7^th International Meeting on Metabotropic Glutamate Receptors, Taormina, Sicily, Italy, 2011.
62. Dickerson JW, Thompson AD, Jones CK, Niswender CM, Hopkins CR, Lindsley CW, Conn PJ. Co-administration of an mGlu4 positive allosteric modulator and the A2A antagonist preladenant improved efficacy in preclinical models of Parkinson’s disease. Society for Neuroscience abstracts, 2011.

 

63. Digby GJ, Utley TJ, Walker AG, Sheffler CJ, Xiang Z, Plumley H, Davis AA, Byun NE, Niswender CM, Jones CK, Lindsley CW, Conn PJ. Characterization of M1-selective partial agonists VU0364572 and VU0357017: evidence for brain-region specific electrophysiological and behavioral effects. Society for Neuroscience abstracts, 2011.

 

64. Klein MT, Digby GJ, Pancani T, Niswender C, Tarr C, Poslusney M, Melancon BJ, Wood MR, Lindsley CW, Conn PJ. Biasing acetylcholine signaling at human M4 muscarinic receptors: Effects of novel positive allosteric modulators. Society for Neuroscience abstracts, 2012.

 

65. Rook JM, Noetzel MJ, Pouliot WA, Bridges TM, Vinson PN, Zhou Y, Gogliotti RD, Manka JT, Stauffer SR, Niswender CM, Dudek FE, Daniels JS, Jones CK, Lindsely CW, Conn PJ. Molecular actions of positive allosteric agonists of mGlu5 determine efficacy versus adverse effect liability in animal models. Society for Neuroscience abstracts, 2012.

 

66. Dickerson JW, Nedelcovych MT, Stauffer SR, Hopkins CR, Niswender CM, Lindsley CW, Jones CK, Conn PJ. Effects of metabotropic glutamate receptor activation on cytokine release and cognition during neuroinflammation. Society for Neuroscience abstracts, 2012.

 

67. Goshal A, Pouget P, Byun N, Stauffer SR, Rook JM, Rodriguez AL, Niswender CM, Jones CK, Lindsley CW, Conn PJ. Effects of metabotropic glutamate receptor 5 activation on neurophysiological sensory processing in vivo: Implications in Schizophrenia. Society for Neuroscience abstracts, 2012.

 

68. Noetzel M, Gregory KJ, Vinson PN, Manka JT, Stauffer SR, Xiang Z, Daniels JS, Niswender CM, Lindsley CW, Conn PJ. Characterization of a potent and efficacious metabotropic glutamate receptor 5 positive allosteric modulator from the CPPHA series. Society for Neuroscience abstracts, 2012.

 

69. Gogliotti RG, Klar R, Zamorano M, Rook JM, Conn PJ, Niswender CM. mGlu5 positive allosteric modulation as a therapeutic strategy for Rett syndrome: weighing the risks and the rewards. Cold Spring Harbor Conference “Wiring the Brain”, 2013.

 

70. Kaufman, Romaine L, Days E, Pascual C, Yang L, Zou B, Malik A, Du Y, Sliwoski G, Morrison R, Denton J, Niswender C, Daniels S, Sulikowski G, Xie XS, Lindsley C, Weaver C. Discovery and characterization of ML297, a novel, in vivo active small molecule activator of G-protein-coupled in ward rectifying potassium (GIRK) channels. Society for Neuroscience abstracts, 2013.

 

71. Gentry PR, Kokubo M, Foster DJ, Bridges TM, Niswender CM, Daniels JS, Conn PJ, Wood MR, Lindsley CW. Discovery, synthesis, and pharmacological characterization of novel, highly selective M₅ allosteric modulators. Society for Neuroscience abstracts, 2013.

 

72. Ghoshal A, Rook JM, Johnson KA, Lv X, Dickerson JW, Lambert Collier RL, Vinson PN, Stauffer SR, Jones CK, Niswender CM, Lindsley CW, Xiang Z, Conn PJ. Stimulus bias of metabotropic glutamate receptor 5 allosteric modulators-impact on CNS effects and implications for therapeutic use. Society for Neuroscience abstracts, 2013.

 

73. Noetzel M, Yin S, Zamorano R, Johnson KA, Conn PJ, Niswender CM. Receptor dimerization changed the ability of mGlu4 positive allosteric modulators to potentiate L-AP4-induced responses. Society for Neuroscience abstracts, 2013.

 

74. Rook JM, Walker AG, Huan Q, Stauffer SR, Niswender CM, Daniels JS, Jones CK, Lindsley CW, Conn PJ. Allosteric modulators of muscarinic acetylcholine and metabotropic glutamate receptors as promising therapeutic strategies for cognition enhancement in Alzheimer’s disease. Society for Neuroscience abstracts, 2013.

 

75. Klar R, Gogliotti RG, Zamorano R, Walker AG, Xiang Z, Conn PJ, Niswender CM. Activation of metabotropic glutamate receptor 7 (mGlu7) rescues hippocampal synaptic plasticity in a mouse model of Rett syndrome. International Rett Syndrome Foundation Symposium, 2014.

 

76. Gogliotti RG, Klar R, Ghoshal A, Zamorano R, Rook J, Conn PJ, Niswender CM. The development of mGlu5 positive allosteric modulators as Rett Syndrome therapeutics. International Rett Syndrome Foundation Symposium, 2014.

 

77. Gogliotti R, Klar R, Zamorano R, Rook J, Walker A, Xiang Z, Conn PJ, Niswender CM. Metabotropic glutamate receptor potentiation as a therapeutic direction in Rett syndrome. International Rett Syndrome Foundation Symposium, 2014.

 

78. Gogliotti RG, Klar R, Ghoshal A, Zamorano R, Rook J, Conn PJ, Niswender CM. The development of mGlu5 positive allosteric modulators as Rett Syndrome therapeutics. 8^th International Congress on Metabotropic Glutamate Receptors, 2014.

 

79. Klar R, Gogliotti RG, Zamorano R, Walker AG, Xiang Z, Conn PJ, Niswender CM. Metabotropic glutamate receptor 7: a novel target for the treatment of Rett syndrome. 8^th International Congress on Metabotropic Glutamate Receptors, 2014.

 

80. Klar R, Gogliotti RG, Zamorano R, Walker AG, Xiang Z, Conn PJ, Niswender CM. Activation of mGlu₇ is Critical for Hippocampal Plasticity and is a Potential Therapeutic Target for the Treatment of Rett Syndrome. 8^th International Congress on Metabotropic Glutamate Receptors, 2014.

 

81. Ghoshal A, Rook JM, Dickerson JW, Morrison RD, Stauffer SR, Jones CK, Daniels JS, Niswender CM, Lindsley CW, Conn PJ. Evaluation of the therapeutic efficacy of M₁ muscarinic acetylcholine receptor potentiation in chronic phencyclidine treated mouse model of schizophrenia. Society for Neuroscience abstracts, 2014.

 

82. Noetzel MJ, Rook JM, Lamsal A, Morrison RD, Cho HP, Niswender CM, Daniels JS, Stauffer SR, Lindsley CW, Conn PJ. M1 muscarinic receptor expression levels influence the effect of positive allosteric modulators. Society for Neuroscience abstracts, 2014.

 

83. Fisher NM, Gogliotti RG, Klar R, Zamorano R, Stansley BJ, Walker AG, Blobaum AL, Engers D, Hopkins CR, Daniels JS, Lindsley CW, Xiang Z, Conn PJ, and Niswender C.M. Therapeutic potential of mGlu₇ in the treatment of MeCP2-Related Disorders. Vanderbilt Kennedy Center Science Day, 2015.

 

84. Stansley BJ, Gogliotti RG, Klar R, Fisher NM, Emmitte, KA, Lindsley C, Conn PJ, Niswender CM. Therapeutic potential of mGlu₃ antagonism in correcting synaptic plasticity defects in a mouse model of MECP2 Duplication Syndrome. Vanderbilt Kennedy Center Science Day, 2015.

 

85. Klar R, Gogliotti RG, Zamorano R, Walker AG, Xiang Z, Conn PJ, Niswender CM. Activation of mGlu₇ is Critical for Hippocampal Plasticity and is a Potential Therapeutic Target for the Treatment of Rett Syndrome. Society for Neuroscience, 2015.

 

86. Gogliotti RG, Klar R, Ghoshal A, Zamorano R, Rook JM, Stauffer SR, Malosh C, Vinson PN, Jones CK, Lindsley CW, Conn PJ, Niswender CM. A novel mGlu₅ positive allosteric modulator improves phenotype and rescues synaptic plasticity defects in a mouse model of Rett syndrome. Society for Neuroscience, 2015.

 

87. Gogliotti RG, Senter RK, Ghoshal A, Zamorano R, Rook JM, Stauffer SR, Malosh C, Vinson P, Jones CK, Lindsley CW, Conn PJ, Niswender, CM. mGlu₅ positive allosteric modulators as a therapeutic strategy for Rett syndrome. Vanderbilt Kennedy Center Science Day, Nashville, TN September 2015.

 

88. Stansley BJ, Gogliotti RG, Klar R, Fisher N, Emmitte K, Lindsley C, Conn PJ, and Niswender CM. mGlu₃ negative allosteric modulation corrects hippocampal synaptic plasticity impairments in a model of MECP2 Duplication syndrome. Vanderbilt Kennedy Center Science Day, Nashville, TN, September 2015.

 

89. Stansley BJ, Gogliotti RG, Klar R, Fisher N, Loch M, Emmitte K, Lindsley C, Conn PJ, and Niswender CM. Therapeutic potential of mGlu₃ antagonism in correcting synaptic plasticity defects in a mouse model of MECP2 Duplication Syndrome. Neuropharmacology Conference, November 2015.

 

90. Fisher NM, Gogliotti RG, Klar R, Zamorano R, Stansley BJ, Walker AG, Blobaum AL, Engers D, Hopkins CR, Daniels JS, Lindsley CW, Xiang Z, Jones CK, Conn PJ, Niswender CM. Therapeutic potential of mGlu₇ in the treatment of MECP2-related disorders. Neuropharmacology Conference, November 2015.

 

91. Stansley BJ, Gogliotti RG, Fisher N, Loch M, Emmitte K, Lindsley C, Conn PJ, and Niswender CM. The therapeutic potential of mGlu₃ antagonism in correcting synaptic plasticity defects in a mouse model of MECP2 Duplication syndrome. Experimental Biology/American Society for Pharmacology and Experimental Therapeutics, April 2016.

 

92. Stansley BJ, Gogliotti RG, Fisher N, Loch M, Emmitte K, Lindsley C, Conn PJ, and Niswender CM. The therapeutic potential of mGlu₃ modulation in MECP2-related disorders. Rett Syndrome Symposium, June 2016.

 

93. Fisher NM, Gogliotti RG, Senter R, Stansley BJ, Gould RG, Walker AG, Zamorano R, Adams JJ, Blobaum AL, Engers S, Hopkins CR, Lindsley CW, Xiang Z, Jones CK, Conn PJ, Niswender CM. Metabotropic glutamate receptor 7 as a therapeutic target for MECP2-related disorders. Rett Syndrome Symposium, June 2016.

 

94. Gogliotti RG, Senter RK, Ghoshal A, Zamorano R, Rook JM, Stauffer SR, Malosh C, Vinson P, Jones CK, Lindsley CW, Conn PJ, Niswender, CM. mGlu₅ positive allosteric modulators as a therapeutic strategy for Rett syndrome. Rett Syndrome Symposium, June 2016

 

95. Niswender CM, Gogliotti RG, Fisher NM, Senter RK, Gould RW, Adams JJ, Stansley BJ, Walker AG, Zamorano R, Blobaum AL, Engers DW, Hopkins CR, Lindsley CW, Conn PJ. Society for Neuroscience, November 2016.

 

96. Moehle MS, Pancani T, Byun NE, Xiang Zm, Wess J, Rook MR, Niswender CM, Jones CK, Lindsley CW, Conn PJ. Activation in the SNr evokes GABA release and increased motor activity and is tonically inhibited by M₄signaling. Society for Neuroscience, November 2016.

 

 

***Best poster winner at respective conference

 

JOURNAL ARTICLES (1-183)

 

 

1. Aldrich, L. N., Lebois, E. P., Lewis, L. M., Nalywajko, N. T., Niswender, C. M., Weaver, C. D., Conn, P. J., and Lindsley, C. W. (2009) MAOS ls for the general synthesis and lead optimization of 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines. Tetrahedron Lett 50, 212-215
2. Alizadeh, A., Fitch, K. R., Niswender, C. M., McKnight, G. S., and Barsh, G. S. (2008) Melanocyte-lineage expression of Cre recombinase using Mitf regulatory elements. Pigment Cell Melanoma Res 21, 63-69
3. Amato, R. J., Felts, A. S., Rodriguez, A. L., Venable, D. F., Morrison, R. D., Byers, F. W., Daniels, J. S., Niswender, C. M., Conn, P. J., Lindsley, C. W., Jones, C. K., and Emmitte, K. A. (2013) Substituted 1-Phenyl-3-(pyridin-2-yl)urea negative allosteric modulators of mGlu5: discovery of a new tool compound VU0463841 with activity in rat models of cocaine addiction. ACS Chem Neurosci 4, 1217-1228
4. Ayala, J. E., Niswender, C. M., Luo, Q., Banko, J. L., and Conn, P. J. (2008) Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated. Neuropharmacology 54, 804-814
5. Backstrom, J. R., Chang, M. S., Chu, H., Niswender, C. M., and Sanders-Bush, E. (1999) Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD). Neuropsychopharmacology 21, 77S-81S
6. Bartolome-Nebreda, J. M., Conde-Ceide, S., Delgado, F., Iturrino, L., Pastor, J., Pena, M. A., Trabanco, A. A., Tresadern, G., Wassvik, C. M., Stauffer, S. R., Jadhav, S., Gogi, K., Vinson, P. N., Noetzel, M. J., Days, E., Weaver, C. D., Lindsley, C. W., Niswender, C. M., Jones, C. K., Conn, P. J., Rombouts, F., Lavreysen, H., Macdonald, G. J., Mackie, C., and Steckler, T. (2013) Dihydrothiazolopyridone derivatives as a novel family of positive allosteric modulators of the metabotropic glutamate 5 (mGlu5) receptor. J Med Chem 56, 7243-7259
7. Bates, B. S., Rodriguez, A. L., Felts, A. S., Morrison, R. D., Venable, D. F., Blobaum, A. L., Byers, F. W., Lawson, K. P., Daniels, J. S., Niswender, C. M., Jones, C. K., Conn, P. J., Lindsley, C. W., and Emmitte, K. A. (2014) Discovery of VU0431316: a negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. Bioorg Med Chem Lett 24, 3307-3314
8. Bender, A. M., Weiner, R. L., Luscombe, V. B., Ajmera, S., Cho, H. P., Chang, S., Zhan, X., Rodriguez, A. L., Niswender, C. M., Engers, D. W., Bridges, T. M., Conn, P. J., and Lindsley, C. W. (2017) Discovery and optimization of 3-(4-aryl/heteroarylsulfonyl)piperazin-1-yl)-6-(piperidin-1-yl)pyridazines as novel, CNS penetrant pan-muscarinic antagonists. Bioorg Med Chem Lett 27, 3576-3581
9. Bender, A. M., Weiner, R. L., Luscombe, V. B., Cho, H. P., Niswender, C. M., Engers, D. W., Bridges, T. M., Conn, P. J., and Lindsley, C. W. (2017) Synthesis and evaluation of 4,6-disubstituted pyrimidines as CNS penetrant pan-muscarinic antagonists with a novel chemotype. Bioorg Med Chem Lett 27, 2479-2483
10. Berg, K. A., Cropper, J. D., Niswender, C. M., Sanders-Bush, E., Emeson, R. B., and Clarke, W. P. (2001) RNA-editing of the 5-HT(2C) receptor alters agonist-receptor-effector coupling specificity. Br J Pharmacol 134, 386-392
11. Blobaum, A. L., Bridges, T. M., Byers, F. W., Turlington, M. L., Mattmann, M. E., Morrison, R. D., Mackie, C., Lavreysen, H., Bartolome, J. M., Macdonald, G. J., Steckler, T., Jones, C. K., Niswender, C. M., Conn, P. J., Lindsley, C. W., Stauffer, S. R., and Daniels, J. S. (2013) Heterotropic activation of the midazolam hydroxylase activity of CYP3A by a positive allosteric modulator of mGlu5: in vitro to in vivo translation and potential impact on clinically relevant drug-drug interactions. Drug Metab Dispos 41, 2066-2075
12. Bridges, T. M., Marlo, J. E., Niswender, C. M., Jones, C. K., Jadhav, S. B., Gentry, P. R., Plumley, H. C., Weaver, C. D., Conn, P. J., and Lindsley, C. W. (2009) 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. J Med Chem 52, 3445-3448
13. Bridges, T. M., Niswender, C. M., Jones, C. K., Lewis, L. M., Weaver, C. D., Wood, M. R., Daniels, J. S., Conn, P. J., and Lindsley, C. W. (2010) Discovery of a Highly Selective in vitro and in vivo M4 Positive Allosteric Modulator (PAM) Series with Greatly Improved Human Receptor Activity.
14. Bridges, T. M., Rook, J. M., Noetzel, M. J., Morrison, R. D., Zhou, Y., Gogliotti, R. D., Vinson, P. N., Xiang, Z., Jones, C. K., Niswender, C. M., Lindsley, C. W., Stauffer, S. R., Conn, P. J., and Daniels, J. S. (2013) Biotransformation of a novel positive allosteric modulator of metabotropic glutamate receptor subtype 5 contributes to seizure-like adverse events in rats involving a receptor agonism-dependent mechanism. Drug Metab Dispos 41, 1703-1714
15. Bubser, M., Bridges, T. M., Dencker, D., Gould, R. W., Grannan, M., Noetzel, M. J., Lamsal, A., Niswender, C. M., Daniels, J. S., Poslusney, M. S., Melancon, B. J., Tarr, J. C., Byers, F. W., Wess, J., Duggan, M. E., Dunlop, J., Wood, M. W., Brandon, N. J., Wood, M. R., Lindsley, C. W., Conn, P. J., and Jones, C. K. (2014) Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci 5, 920-942
16. Burns, C. M., Chu, H., Rueter, S. M., Hutchinson, L. K., Canton, H., Sanders-Bush, E., and Emeson, R. B. (1997) Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387, 303-308
17. Cheung, Y. Y., Zamorano, R., Blobaum, A. L., Weaver, C. D., Conn, P. J., Lindsley, C. W., Niswender, C. M., and Hopkins, C. R. (2011) Solution-phase parallel synthesis and SAR of homopiperazinyl analogs as positive allosteric modulators of mGlu(4). ACS Comb Sci 13, 159-165
18. Cho, H. P., Engers, D. W., Venable, D. F., Niswender, C. M., Lindsley, C. W., Conn, P. J., Emmitte, K. A., and Rodriguez, A. L. (2014) A novel class of succinimide-derived negative allosteric modulators of metabotropic glutamate receptor subtype 1 provides insight into a disconnect in activity between the rat and human receptors. ACS Chem Neurosci 5, 597-610
19. Cho, H. P., Garcia-Barrantes, P. M., Brogan, J. T., Hopkins, C. R., Niswender, C. M., Rodriguez, A. L., Venable, D. F., Morrison, R. D., Bubser, M., Daniels, J. S., Jones, C. K., Conn, P. J., and Lindsley, C. W. (2014) Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenics. ACS Chem Biol 9, 2334-2346
20. Conde-Ceide, S., Alcazar, J., Alonso de Diego, S. A., Lopez, S., Martin-Martin, M. L., Martinez-Viturro, C. M., Pena, M. A., Tong, H. M., Lavreysen, H., Mackie, C., Bridges, T. M., Daniels, J. S., Niswender, C. M., Jones, C. K., Macdonald, G. J., Steckler, T., Conn, P. J., Stauffer, S. R., Lindsley, C. W., and Bartolome-Nebreda, J. M. (2016) Preliminary investigation of 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one derivatives as a novel series of mGlu5 receptor positive allosteric modulators with efficacy in preclinical models of schizophrenia. Bioorg Med Chem Lett 26, 429-434
21. Conde-Ceide, S., Martinez-Viturro, C. M., Alcazar, J., Garcia-Barrantes, P. M., Lavreysen, H., Mackie, C., Vinson, P. N., Rook, J. M., Bridges, T. M., Daniels, J. S., Megens, A., Langlois, X., Drinkenburg, W. H., Ahnaou, A., Niswender, C. M., Jones, C. K., Macdonald, G. J., Steckler, T., Conn, P. J., Stauffer, S. R., Bartolome-Nebreda, J. M., and Lindsley, C. W. (2015) Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia. ACS Med Chem Lett 6, 716-720
22. Conn, P. J., Lindsley, C. W., Meiler, J., and Niswender, C. M. (2014) Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders. Nat Rev Drug Discov 13, 692-708
23. Conn, P. J., and Niswender, C. M. (2006) mGluR7’s lucky number. Proc Natl Acad Sci U S A 103, 251-252
24. Days, E., Kaufmann, K., Romaine, I., Niswender, C., Lewis, M., Utley, T., Du, Y., Sliwoski, G., Morrison, R., Dawson, E. S., Engers, J. L., Denton, J., Daniels, J. S., Sulikowski, G. A., Lindsley, C. W., and Weaver, C. D. (2010) Discovery and Characterization of a Selective Activator of the G-Protein Activated Inward-Rectifying Potassium (GIRK) Channel.
25. Digby, G. J., Noetzel, M. J., Bubser, M., Utley, T. J., Walker, A. G., Byun, N. E., Lebois, E. P., Xiang, Z., Sheffler, D. J., Cho, H. P., Davis, A. A., Nemirovsky, N. E., Mennenga, S. E., Camp, B. W., Bimonte-Nelson, H. A., Bode, J., Italiano, K., Morrison, R., Daniels, J. S., Niswender, C. M., Olive, M. F., Lindsley, C. W., Jones, C. K., and Conn, P. J. (2012) Novel allosteric agonists of M1 muscarinic acetylcholine receptors induce brain region-specific responses that correspond with behavioral effects in animal models. J Neurosci 32, 8532-8544
26. Digby, G. J., Utley, T. J., Lamsal, A., Sevel, C., Sheffler, D. J., Lebois, E. P., Bridges, T. M., Wood, M. R., Niswender, C. M., Lindsley, C. W., and Conn, P. J. (2012) Chemical modification of the M(1) agonist VU0364572 reveals molecular switches in pharmacology and a bitopic binding mode. ACS Chem Neurosci 3, 1025-1036
27. Engers, D. W., Blobaum, A. L., Gogliotti, R. D., Cheung, Y. Y., Salovich, J. M., Garcia-Barrantes, P. M., Daniels, J. S., Morrison, R., Jones, C. K., Soars, M. G., Zhuo, X., Hurley, J., Macor, J. E., Bronson, J. J., Conn, P. J., Lindsley, C. W., Niswender, C. M., and Hopkins, C. R. (2016) Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4). ACS Chem Neurosci 7, 1192-1200
28. Engers, D. W., Field, J. R., Le, U., Zhou, Y., Bolinger, J. D., Zamorano, R., Blobaum, A. L., Jones, C. K., Jadhav, S., Weaver, C. D., Conn, P. J., Lindsley, C. W., Niswender, C. M., and Hopkins, C. R. (2011) Discovery, synthesis, and structure-activity relationship development of a series of N-(4-acetamido)phenylpicolinamides as positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)) with CNS exposure in rats. J Med Chem 54, 1106-1110
29. Engers, D. W., Gentry, P. R., Williams, R., Bolinger, J. D., Weaver, C. D., Menon, U. N., Conn, P. J., Lindsley, C. W., Niswender, C. M., and Hopkins, C. R. (2010) Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS). Bioorg Med Chem Lett 20, 5175-5178
30. Engers, D. W., Jones, C. K., Bubser, M., Thompson, A. D., Blobaum, A. L., Sheffler, D. J., Zamorano, R., Carrington, S. J. S., Bridges, T. M., Morrison, R. D., Daniels, J. S., Conn, P. J., Lindsley, C. W., Niswender, C. M., and Hopkins, C. R. (2010) Discovery of a novel metabotropic glutamate receptor 4 (mGlu4) positive allosteric modulator (PAM) extended probe: Characterization of ML292, a potent and selective mGlu4 PAM which produces efficacy alone or in combination with L-DOPA in preclinical rodent models of Parkinson’s disease.
31. Engers, D. W., Niswender, C. M., Weaver, C. D., Jadhav, S., Menon, U. N., Zamorano, R., Conn, P. J., Lindsley, C. W., and Hopkins, C. R. (2009) Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs). J Med Chem 52, 4115-4118
32. Engers, J. L., Rodriguez, A. L., Konkol, L. C., Morrison, R. D., Thompson, A. D., Byers, F. W., Blobaum, A. L., Chang, S., Venable, D. F., Loch, M. T., Niswender, C. M., Daniels, J. S., Jones, C. K., Conn, P. J., Lindsley, C. W., and Emmitte, K. A. (2015) Discovery of a Selective and CNS Penetrant Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 3 with Antidepressant and Anxiolytic Activity in Rodents. J Med Chem 58, 7485-7500
33. Felts, A. S., Rodriguez, A. L., Blobaum, A. L., Morrison, R. D., Bates, B. S., Thompson Gray, A., Rook, J. M., Tantawy, M. N., Byers, F. W., Chang, S., Venable, D. F., Luscombe, V. B., Tamagnan, G. D., Niswender, C. M., Daniels, J. S., Jones, C. K., Conn, P. J., Lindsley, C. W., and Emmitte, K. A. (2017) Discovery of N-(5-Fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (VU0424238): A Novel Negative Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 5 Selected for Clinical Evaluation. J Med Chem 60, 5072-5085
34. Felts, A. S., Rodriguez, A. L., Morrison, R. D., Venable, D. F., Blobaum, A. L., Byers, F. W., Daniels, J. S., Niswender, C. M., Jones, C. K., Conn, P. J., Lindsley, C. W., and Emmitte, K. A. (2016) N-Alkylpyrido[1′,2′:1,5]pyrazolo-[4,3-d]pyrimidin-4-amines: A new series of negative allosteric modulators of mGlu1/5 with CNS exposure in rodents. Bioorg Med Chem Lett 26, 1894-1900
35. Felts, A. S., Rodriguez, A. L., Morrison, R. D., Venable, D. F., Manka, J. T., Bates, B. S., Blobaum, A. L., Byers, F. W., Daniels, J. S., Niswender, C. M., Jones, C. K., Conn, P. J., Lindsley, C. W., and Emmitte, K. A. (2013) Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. Bioorg Med Chem Lett 23, 5779-5785
36. Felts, A. S., Rodriguez, A. L., Smith, K. A., Engers, J. L., Morrison, R. D., Byers, F. W., Blobaum, A. L., Locuson, C. W., Chang, S., Venable, D. F., Niswender, C. M., Daniels, J. S., Conn, P. J., Lindsley, C. W., and Emmitte, K. A. (2015) Design of 4-Oxo-1-aryl-1,4-dihydroquinoline-3-carboxamides as Selective Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 2. J Med Chem 58, 9027-9040
37. Foster, D. J., Gentry, P. R., Lizardi-Ortiz, J. E., Bridges, T. M., Wood, M. R., Niswender, C. M., Sulzer, D., Lindsley, C. W., Xiang, Z., and Conn, P. J. (2014) M5 receptor activation produces opposing physiological outcomes in dopamine neurons depending on the receptor’s location. J Neurosci 34, 3253-3262
38. Foster, D. J., Wilson, J. M., Remke, D. H., Mahmood, M. S., Uddin, M. J., Wess, J., Patel, S., Marnett, L. J., Niswender, C. M., Jones, C. K., Xiang, Z., Lindsley, C. W., Rook, J. M., and Conn, P. J. (2016) Antipsychotic-like Effects of M4 Positive Allosteric Modulators Are Mediated by CB2 Receptor-Dependent Inhibition of Dopamine Release. Neuron 91, 1244-1252
39. Garcia, R. C., Dati, L. M., Torres, L. H., da Silva, M. A., Udo, M. S., Abdalla, F. M., da Costa, J. L., Gorjao, R., Afeche, S. C., Yonamine, M., Niswender, C. M., Conn, P. J., Camarini, R., Sandoval, M. R., and Marcourakis, T. (2015) M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product. Sci Rep 5, 17555
40. Garcia-Barrantes, P. M., Cho, H. P., Blobaum, A. L., Niswender, C. M., Conn, P. J., and Lindsley, C. W. (2015) Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 1: SAR of modifications to the central aryl core. Bioorg Med Chem Lett 25, 5107-5110
41. Garcia-Barrantes, P. M., Cho, H. P., Blobaum, A. L., Niswender, C. M., Conn, P. J., and Lindsley, C. W. (2016) Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs. Bioorg Med Chem Lett 26, 1869-1872
42. Garcia-Barrantes, P. M., Cho, H. P., Metts, A. M., Blobaum, A. L., Niswender, C. M., Conn, P. J., and Lindsley, C. W. (2016) Lead optimization of the VU0486321 series of mGlu(1) PAMs. Part 2: SAR of alternative 3-methyl heterocycles and progress towards an in vivo tool. Bioorg Med Chem Lett 26, 751-756
43. Garcia-Barrantes, P. M., Cho, H. P., Niswender, C. M., Byers, F. W., Locuson, C. W., Blobaum, A. L., Xiang, Z., Rook, J. M., Conn, P. J., and Lindsley, C. W. (2015) Development of Novel, CNS Penetrant Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics. J Med Chem 58, 7959-7971
44. Garcia-Barrantes, P. M., Cho, H. P., Starr, T. M., Blobaum, A. L., Niswender, C. M., Conn, P. J., and Lindsley, C. W. (2016) Re-exploration of the mGlu1 PAM Ro 07-11401 scaffold: Discovery of analogs with improved CNS penetration despite steep SAR. Bioorg Med Chem Lett 26, 2289-2292
45. Gentry, P. R., Bridges, T. M., Daniels, J. S., Lamsal, A., Vinson, P. N., Niswender, C. M., Hodder, P. S., Rosen, H., Conn, P. J., Engers, J., Lindsley, C. W., and Wood, M. R. (2010) Development and characterization of a highly selective M5 PAM probe molecule with improved potency.
46. Gentry, P. R., Bridges, T. M., Lamsal, A., Vinson, P. N., Smith, E., Chase, P., Hodder, P. S., Engers, J. L., Niswender, C. M., Daniels, J. S., Conn, P. J., Wood, M. R., and Lindsley, C. W. (2013) Discovery of ML326: The first sub-micromolar, selective M5 PAM. Bioorg Med Chem Lett 23, 2996-3000
47. Gentry, P. R., Kokubo, M., Bridges, T. M., Cho, H. P., Smith, E., Chase, P., Hodder, P. S., Utley, T. J., Rajapakse, A., Byers, F., Niswender, C. M., Morrison, R. D., Daniels, J. S., Wood, M. R., Conn, P. J., and Lindsley, C. W. (2014) Discovery, synthesis and characterization of a highly muscarinic acetylcholine receptor (mAChR)-selective M5-orthosteric antagonist, VU0488130 (ML381): a novel molecular probe. ChemMedChem 9, 1677-1682
48. Gentry, P. R., Kokubo, M., Bridges, T. M., Daniels, J. S., Niswender, C. M., Smith, E., Chase, P., Hodder, P. S., Rosen, H., Conn, P. J., Engers, J., Brewer, K. A., Lindsley, C. W., and Wood, M. R. (2010) Development of the First CNS penetrant M5 Positive Allosteric Modulator (PAM) Based on a Novel, non-Isatin Core.
49. Gentry, P. R., Kokubo, M., Bridges, T. M., Daniels, J. S., Niswender, C. M., Smith, E., Chase, P., Hodder, P. S., Rosen, H., Conn, P. J., Engers, J., Brewer, K. A., Wood, M. R., and Lindsley, C. W. (2010) Development of a Novel, Orthosteric M5 Antagonist Possessing a High Degree of Muscarinic Subtype Selectivity.
50. Gentry, P. R., Kokubo, M., Bridges, T. M., Daniels, J. S., Niswender, C. M., Smith, E., Chase, P., Hodder, P. S., Rosen, H., Conn, P. J., Engers, J., Brewer, K. A., Wood, M. R., and Lindsley, C. W. (2010) Development of the First Potent, Selective and CNS penetrant M5 Negative Allosteric Modulator (NAM).
51. Gentry, P. R., Kokubo, M., Bridges, T. M., Kett, N. R., Harp, J. M., Cho, H. P., Smith, E., Chase, P., Hodder, P. S., Niswender, C. M., Daniels, J. S., Conn, P. J., Wood, M. R., and Lindsley, C. W. (2013) Discovery of the first M5-selective and CNS penetrant negative allosteric modulator (NAM) of a muscarinic acetylcholine receptor: (S)-9b-(4-chlorophenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydro-1H-imidazo[2,1-a]isoi ndol-5(9bH)-one (ML375). J Med Chem 56, 9351-9355
52. Gentry, P. R., Kokubo, M., Bridges, T. M., Noetzel, M. J., Cho, H. P., Lamsal, A., Smith, E., Chase, P., Hodder, P. S., Niswender, C. M., Daniels, J. S., Conn, P. J., Lindsley, C. W., and Wood, M. R. (2014) Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4- carboxamide (ML380). J Med Chem 57, 7804-7810
53. Ghoshal, A., Rook, J. M., Dickerson, J. W., Roop, G. N., Morrison, R. D., Jalan-Sakrikar, N., Lamsal, A., Noetzel, M. J., Poslusney, M. S., Wood, M. R., Melancon, B. J., Stauffer, S. R., Xiang, Z., Daniels, J. S., Niswender, C. M., Jones, C. K., Lindsley, C. W., and Conn, P. J. (2016) Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model. Neuropsychopharmacology 41, 598-610
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