Colleen M. Niswender, Ph.D.

Research Professor

colleen.niswender@vanderbilt.edu
Faculty Appointments
Research Professor of Pharmacology
Education
Ph.D., Pharmacology, Vanderbilt University, Nashville, TennesseeB.S., Pharmacy, University of Toledo, Toledo, Ohio
Office Address
12478C MRB IV/Light Hall
23rd Avenue at Pierce
Nashville, TN 37212-6600
Research Description
I am a Professor of Pharmacology and also currently serve as the Director of Molecular Pharmacology for the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD). My work focuses on high throughput screening, assay development, and in vitro pharmacology experiments to investigate the effects of novel modulators on cellular signaling pathways. I have been or am currently involved in each of the main VCNDD collaborations, including those partnered with the Michael J. Fox Foundation, Johnson and Johnson, Astrazeneca, Lundbeck, the William K. Warren Foundation, and the NIH. One of these projects has progressed to a clinical trial. I am also the Biology Team Leader for the development of potential clinical candidates for metabotropic glutamate receptor 4 (mGlu4) modulation as a treatment of Parkinson's disease, a program that is now moving into IND-enabling work. Most recently, I have initiated a new area of study for the VCNDD: that of disorders related to mutations or overexpression of the protein Methyl CpG Binding Protein 2 (MeCP2). Mutations in the MECP2 gene cause the neurodevelopmental disorder, Rett syndrome, while gene duplications cause MECP2 Duplication syndrome. These disorders result in a constellation of symptoms, beginning in childhood, including regression and loss of previously acquired skills, stereotypic movements, difficulty in walking and speaking, apneas, recurrent infections, and debilitating seizures. It is our goal to explore the therapeutic potential of modulation of metabotropic glutamate receptors 3, 5 and 7, as well as the M1 and M4 muscarinic receptors, in the treatment of Rett and MECP2 Duplication symptoms using small molecule allosteric modulators.
Research Keywords
Neuroscience receptor pharmacology and cellular signaling Rett syndrome MECP2 Duplication syndrome Parkinson's disease Schizophrenia Autism Neurofibromatosis Depression
Publications
O'Brien DE, Shaw DM, Cho HP, Cross AJ, Wesolowski SS, Felts AS, Bergare J, Elmore CS, Lindsley CW, Niswender CM, Conn PJ. Differential Pharmacology and Binding of mGlu2 Receptor Allosteric Modulators. Mol. Pharmacol [print-electronic]. 2018 Mar 3/15/2018; PMID: 29545267, PII: mol.117.110114, DOI: 10.1124/mol.117.110114, ISSN: 1521-0111.

Gogliotti R, Fisher N, Stansley B, Jones C, Lindsley C, Conn J, Niswender C. Total RNA-sequencing of Rett Syndrome Autopsy Samples Identifies the M4 Muscarinic Receptor as a Novel Therapeutic Target. J. Pharmacol. Exp. Ther [print-electronic]. 2018 Mar 3/9/2018; PMID: 29523700, PII: jpet.117.246991, DOI: 10.1124/jpet.117.246991, ISSN: 1521-0103.

Ponnazhagan R, Harms AS, Thome AD, Jurkuvenaite A, Gogliotti R, Niswender CM, Conn PJ, Standaert DG. The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia. J Neuroimmune Pharmacol [print-electronic]. 2016 Jun; 11(2): 231-7. PMID: 26872456, PMCID: PMC4848139, PII: 10.1007/s11481-016-9655-z, DOI: 10.1007/s11481-016-9655-z, ISSN: 1557-1904.

Gogliotti RG, Senter RK, Rook JM, Ghoshal A, Zamorano R, Malosh C, Stauffer SR, Bridges TM, Bartolome JM, Daniels JS, Jones CK, Lindsley CW, Conn PJ, Niswender CM. MGlu5 positive allosteric modulation normalizes synaptic plasticity defects and motor phenotypes in a mouse model of Rett syndrome. Hum. Mol. Genet [print-electronic]. 2016 Mar 3/2/2016; PMID: 26936821, PII: ddw074, DOI: 10.1093/hmg/ddw074, ISSN: 1460-2083.

Gould RW, Nedelcovych MT, Gong X, Tsai E, Bubser M, Bridges TM, Wood MR, Duggan ME, Brandon NJ, Dunlop J, Wood MW, Ivarsson M, Noetzel MJ, Daniels JS, Niswender CM, Lindsley CW, Conn PJ, Jones CK. State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 - Relation to antipsychotic-like drug effects. Neuropharmacology [print-electronic]. 2016 Mar; 102: 244-53. PMID: 26617071, PII: S0028-3908(15)30180-5, DOI: 10.1016/j.neuropharm.2015.11.016, ISSN: 1873-7064.

Garcia-Barrantes PM, Cho HP, Metts AM, Blobaum AL, Niswender CM, Conn PJ, Lindsley CW. 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 [print-electronic]. 2016 Feb 2/1/2016; 26(3): 751-6. PMID: 26778256, PMCID: PMC4794757, PII: S0960-894X(15)30417-0, DOI: 10.1016/j.bmcl.2015.12.104, ISSN: 1464-3405.

Conde-Ceide S, Alcázar J, Alonso de Diego SA, López S, Martín-Martín ML, Martínez-Viturro CM, Pena MA, Tong HM, Lavreysen H, Mackie C, Bridges TM, Daniels JS, Niswender CM, Jones CK, Macdonald GJ, Steckler T, Conn PJ, Stauffer SR, Lindsley CW, Bartolomé-Nebreda JM. 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 [print-electronic]. 2016 Jan 1/15/2016; 26(2): 429-34. PMID: 26684851, PMCID: PMC4835042, PII: S0960-894X(15)30306-1, DOI: 10.1016/j.bmcl.2015.11.098, ISSN: 1464-3405.

Nickols HH, Yuh JP, Gregory KJ, Morrison RD, Bates BS, Stauffer SR, Emmitte KA, Bubser M, Peng W, Nedelcovych MT, Thompson A, Lv X, Xiang Z, Daniels JS, Niswender CM, Lindsley CW, Jones CK, Conn PJ. VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy. J. Pharmacol. Exp. Ther [print-electronic]. 2016 Jan; 356(1): 123-36. PMID: 26503377, PII: jpet.115.226597, DOI: 10.1124/jpet.115.226597, ISSN: 1521-0103.

Ghoshal A, Rook JM, Dickerson JW, Roop GN, Morrison RD, Jalan-Sakrikar N, Lamsal A, Noetzel MJ, Poslusney MS, Wood MR, Melancon BJ, Stauffer SR, Xiang Z, Daniels JS, Niswender CM, Jones CK, Lindsley CW, Conn PJ. Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model. Neuropsychopharmacology [print-electronic]. 2016 Jan; 41(2): 598-610. PMID: 26108886, PII: npp2015189, DOI: 10.1038/npp.2015.189, ISSN: 1740-634X.

Ghoshal A, Rook JM, Dickerson JW, Roop GN, Morrison RD, Jalan-Sakrikar N, Lamsal A, Noetzel MJ, Poslusney MS, Wood MR, Melancon BJ, Stauffer SR, Xiang Z, Daniels JS, Niswender CM, Jones CK, Lindsley CW, Conn PJ. Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model. Neuropsychopharmacology [print-electronic]. 2016 Jan; 41(2): 598-610. PMID: 26108886, PII: npp2015189, DOI: 10.1038/npp.2015.189, ISSN: 1740-634X.

Senter RK, Ghoshal A, Walker AG, Xiang Z, Niswender CM, Conn PJ. The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies. Curr Neuropharmacol. 2016; 14(5): 455-73. PMID: 27296640, PII: CN-EPUB-66683, ISSN: 1875-6190.

Felts AS, Rodriguez AL, Smith KA, Engers JL, Morrison RD, Byers FW, Blobaum AL, Locuson CW, Chang S, Venable DF, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Emmitte KA. 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 [print-electronic]. 2015 Nov 11/25/2015; 58(22): 9027-40. PMID: 26524606, DOI: 10.1021/acs.jmedchem.5b01371, ISSN: 1520-4804.

Garcia-Barrantes PM, Cho HP, Blobaum AL, Niswender CM, Conn PJ, Lindsley CW. Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 1: SAR of modifications to the central aryl core. Bioorg. Med. Chem. Lett [print-electronic]. 2015 Nov 11/15/2015; 25(22): 5107-10. PMID: 26476971, PII: S0960-894X(15)30121-9, DOI: 10.1016/j.bmcl.2015.10.013, ISSN: 1464-3405.

Malosh C, Turlington M, Bridges TM, Rook JM, Noetzel MJ, Vinson PN, Steckler T, Lavreysen H, Mackie C, Bartolomé-Nebreda JM, Conde-Ceide S, Martínez-Viturro CM, Piedrafita M, Sánchez-Casado MR, Macdonald GJ, Daniels JS, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR. Acyl dihydropyrazolo[1,5-a]pyrimidinones as metabotropic glutamate receptor 5 positive allosteric modulators. Bioorg. Med. Chem. Lett [print-electronic]. 2015 Nov 11/15/2015; 25(22): 5115-20. PMID: 26475522, PMCID: PMC4634704, PII: S0960-894X(15)30118-9, DOI: 10.1016/j.bmcl.2015.10.009, ISSN: 1464-3405.

Pancani T, Foster DJ, Moehle MS, Bichell TJ, Bradley E, Bridges TM, Klar R, Poslusney M, Rook JM, Daniels JS, Niswender CM, Jones CK, Wood MR, Bowman AB, Lindsley CW, Xiang Z, Conn PJ. Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Nov 11/10/2015; 112(45): 14078-83. PMID: 26508634, PMCID: PMC4653197, PII: 1512812112, DOI: 10.1073/pnas.1512812112, ISSN: 1091-6490.

Pancani T, Foster DJ, Moehle MS, Bichell TJ, Bradley E, Bridges TM, Klar R, Poslusney M, Rook JM, Daniels JS, Niswender CM, Jones CK, Wood MR, Bowman AB, Lindsley CW, Xiang Z, Conn PJ. Allosteric activation of M4 muscarinic receptors improve behavioral and physiological alterations in early symptomatic YAC128 mice. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Nov 11/10/2015; 112(45): 14078-83. PMID: 26508634, PMCID: PMC4653197, PII: 1512812112, DOI: 10.1073/pnas.1512812112, ISSN: 1091-6490.

Garcia-Barrantes PM, Cho HP, Niswender CM, Byers FW, Locuson CW, Blobaum AL, Xiang Z, Rook JM, Conn PJ, Lindsley CW. 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 [print-electronic]. 2015 Oct 10/22/2015; 58(20): 7959-71. PMID: 26426481, DOI: 10.1021/acs.jmedchem.5b00727, ISSN: 1520-4804.

Engers JL, Rodriguez AL, Konkol LC, Morrison RD, Thompson AD, Byers FW, Blobaum AL, Chang S, Venable DF, Loch MT, Niswender CM, Daniels JS, Jones CK, Conn PJ, Lindsley CW, Emmitte KA. 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 [print-electronic]. 2015 Sep 9/24/2015; 58(18): 7485-500. PMID: 26335039, DOI: 10.1021/acs.jmedchem.5b01005, ISSN: 1520-4804.

Zhou Y, Malosh C, Conde-Ceide S, Martínez-Viturro CM, Alcázar J, Lavreysen H, Mackie C, Bridges TM, Daniels JS, Niswender CM, Jones CK, Macdonald GJ, Steckler T, Conn PJ, Stauffer SR, Bartolomé-Nebreda JM, Lindsley CW. Further optimization of the mGlu5 PAM clinical candidate VU0409551/JNJ-46778212: Progress and challenges towards a back-up compound. Bioorg. Med. Chem. Lett [print-electronic]. 2015 Sep 9/1/2015; 25(17): 3515-9. PMID: 26183084, PMCID: PMC4535329, PII: S0960-894X(15)00701-5, DOI: 10.1016/j.bmcl.2015.06.096, ISSN: 1464-3405.

Gould RW, Amato RJ, Bubser M, Joffe ME, Nedelcovych MT, Thompson AD, Nickols HH, Yuh JP, Zhan X, Felts AS, Rodriguez AL, Morrison RD, Byers FW, Rook JM, Daniels JS, Niswender CM, Conn PJ, Emmitte KA, Lindsley CW, Jones CK. Partial mGlu5 Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects. Neuropsychopharmacology [print-electronic]. 2015 Aug 8/28/2015; PMID: 26315507, PII: npp2015265, DOI: 10.1038/npp.2015.265, ISSN: 1740-634X.

Smith E, Chase P, Niswender CM, Utley TJ, Sheffler DJ, Noetzel MJ, Lamsal A, Wood MR, Conn PJ, Lindsley CW, Madoux F, Acosta M, Scampavia L, Spicer T, Hodder P. Application of Parallel Multiparametric Cell-Based FLIPR Detection Assays for the Identification of Modulators of the Muscarinic Acetylcholine Receptor 4 (M4). J Biomol Screen [print-electronic]. 2015 Aug; 20(7): 858-68. PMID: 25877150, PMCID: PMC4659430, PII: 1087057115581770, DOI: 10.1177/1087057115581770, ISSN: 1552-454X.

Iderberg H, Maslava N, Thompson AD, Bubser M, Niswender CM, Hopkins CR, Lindsley CW, Conn PJ, Jones CK, Cenci MA. Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia: Comparison between a positive allosteric modulator and an orthosteric agonist. Neuropharmacology [print-electronic]. 2015 Aug; 95: 121-9. PMID: 25749357, PMCID: PMC4466038, PII: S0028-3908(15)00079-9, DOI: 10.1016/j.neuropharm.2015.02.023, ISSN: 1873-7064.

Smith E, Chase P, Niswender CM, Utley TJ, Sheffler DJ, Noetzel MJ, Lamsal A, Wood MR, Conn PJ, Lindsley CW, Madoux F, Acosta M, Scampavia L, Spicer T, Hodder P. Application of Parallel Multiparametric Cell-Based FLIPR Detection Assays for the Identification of Modulators of the Muscarinic Acetylcholine Receptor 4 (M4). J Biomol Screen [print-electronic]. 2015 Aug; 20(7): 858-68. PMID: 25877150, PMCID: PMC4659430, PII: 1087057115581770, DOI: 10.1177/1087057115581770, ISSN: 1552-454X.

Iderberg H, Maslava N, Thompson AD, Bubser M, Niswender CM, Hopkins CR, Lindsley CW, Conn PJ, Jones CK, Cenci MA. Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia: Comparison between a positive allosteric modulator and an orthosteric agonist. Neuropharmacology [print-electronic]. 2015 Aug; 95: 121-9. PMID: 25749357, PMCID: PMC4466038, PII: S0028-3908(15)00079-9, DOI: 10.1016/j.neuropharm.2015.02.023, ISSN: 1873-7064.

Conde-Ceide S, Martínez-Viturro CM, Alcázar J, Garcia-Barrantes PM, Lavreysen H, Mackie C, Vinson PN, Rook JM, Bridges TM, Daniels JS, Megens A, Langlois X, Drinkenburg WH, Ahnaou A, Niswender CM, Jones CK, Macdonald GJ, Steckler T, Conn PJ, Stauffer SR, Bartolomé-Nebreda JM, Lindsley CW. Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia. ACS Med Chem Lett. 2015 Jun 6/11/2015; 6(6): 716-20. PMID: 26157544, PMCID: PMC4492464, DOI: 10.1021/acsmedchemlett.5b00181, ISSN: 1948-5875.

Conde-Ceide S, Martínez-Viturro CM, Alcázar J, Garcia-Barrantes PM, Lavreysen H, Mackie C, Vinson PN, Rook JM, Bridges TM, Daniels JS, Megens A, Langlois X, Drinkenburg WH, Ahnaou A, Niswender CM, Jones CK, Macdonald GJ, Steckler T, Conn PJ, Stauffer SR, Bartolomé-Nebreda JM, Lindsley CW. Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia. ACS Med Chem Lett. 2015 Jun 6/11/2015; 6(6): 716-20. PMID: 26157544, PMCID: PMC4492464, DOI: 10.1021/acsmedchemlett.5b00181, ISSN: 1948-5875.

Rook JM, Xiang Z, Lv X, Ghoshal A, Dickerson JW, Bridges TM, Johnson KA, Foster DJ, Gregory KJ, Vinson PN, Thompson AD, Byun N, Collier RL, Bubser M, Nedelcovych MT, Gould RW, Stauffer SR, Daniels JS, Niswender CM, Lavreysen H, Mackie C, Conde-Ceide S, Alcazar J, Bartolomé-Nebreda JM, Macdonald GJ, Talpos JC, Steckler T, Jones CK, Lindsley CW, Conn PJ. Biased mGlu5-Positive Allosteric Modulators Provide In Vivo Efficacy without Potentiating mGlu5 Modulation of NMDAR Currents. Neuron [print-electronic]. 2015 May 5/20/2015; 86(4): 1029-40. PMID: 25937172, PMCID: PMC4443790, PII: S0896-6273(15)00287-1, DOI: 10.1016/j.neuron.2015.03.063, ISSN: 1097-4199.

Rook JM, Xiang Z, Lv X, Ghoshal A, Dickerson JW, Bridges TM, Johnson KA, Foster DJ, Gregory KJ, Vinson PN, Thompson AD, Byun N, Collier RL, Bubser M, Nedelcovych MT, Gould RW, Stauffer SR, Daniels JS, Niswender CM, Lavreysen H, Mackie C, Conde-Ceide S, Alcazar J, Bartolomé-Nebreda JM, Macdonald GJ, Talpos JC, Steckler T, Jones CK, Lindsley CW, Conn PJ. Biased mGlu5-Positive Allosteric Modulators Provide In Vivo Efficacy without Potentiating mGlu5 Modulation of NMDAR Currents. Neuron [print-electronic]. 2015 May 5/20/2015; 86(4): 1029-40. PMID: 25937172, PMCID: PMC4443790, PII: S0896-6273(15)00287-1, DOI: 10.1016/j.neuron.2015.03.063, ISSN: 1097-4199.

Klar R, Walker AG, Ghose D, Grueter BA, Engers DW, Hopkins CR, Lindsley CW, Xiang Z, Conn PJ, Niswender CM. Activation of Metabotropic Glutamate Receptor 7 Is Required for Induction of Long-Term Potentiation at SC-CA1 Synapses in the Hippocampus. J. Neurosci. 2015 May 5/13/2015; 35(19): 7600-15. PMID: 25972184, PMCID: PMC4429158, PII: 35/19/7600, DOI: 10.1523/JNEUROSCI.4543-14.2015, ISSN: 1529-2401.

Klar R, Walker AG, Ghose D, Grueter BA, Engers DW, Hopkins CR, Lindsley CW, Xiang Z, Conn PJ, Niswender CM. Activation of Metabotropic Glutamate Receptor 7 Is Required for Induction of Long-Term Potentiation at SC-CA1 Synapses in the Hippocampus. J. Neurosci. 2015 May 5/13/2015; 35(19): 7600-15. PMID: 25972184, PMCID: PMC4429158, PII: 35/19/7600, DOI: 10.1523/JNEUROSCI.4543-14.2015, ISSN: 1529-2401.

Martín-Martín ML, Bartolomé-Nebreda JM, Conde-Ceide S, Alonso de Diego SA, López S, Martínez-Viturro CM, Tong HM, Lavreysen H, Macdonald GJ, Steckler T, Mackie C, Bridges TM, Daniels JS, Niswender CM, Noetzel MJ, Jones CK, Conn PJ, Lindsley CW, Stauffer SR. Discovery and SAR of novel series of imidazopyrimidinones and dihydroimidazopyrimidinones as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5). Bioorg. Med. Chem. Lett [print-electronic]. 2015 Mar 3/15/2015; 25(6): 1310-7. PMID: 25683622, PMCID: PMC4399811, PII: S0960-894X(15)00050-5, DOI: 10.1016/j.bmcl.2015.01.038, ISSN: 1464-3405.

Kurata H, Gentry PR, Kokubo M, Cho HP, Bridges TM, Niswender CM, Byers FW, Wood MR, Daniels JS, Conn PJ, Lindsley CW. Further optimization of the M5 NAM MLPCN probe ML375: tactics and challenges. Bioorg. Med. Chem. Lett [print-electronic]. 2015 Feb 2/1/2015; 25(3): 690-4. PMID: 25542588, PMCID: PMC4535335, PII: S0960-894X(14)01289-X, DOI: 10.1016/j.bmcl.2014.11.082, ISSN: 1464-3405.

Rook JM, Tantawy MN, Ansari MS, Felts AS, Stauffer SR, Emmitte KA, Kessler RM, Niswender CM, Daniels JS, Jones CK, Lindsley CW, Conn PJ. Relationship between in vivo receptor occupancy and efficacy of metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro binding profiles. Neuropsychopharmacology [print-electronic]. 2015 Feb; 40(3): 755-65. PMID: 25241804, PMCID: PMC4289965, PII: npp2014245, DOI: 10.1038/npp.2014.245, ISSN: 1740-634X.

Rook JM, Tantawy MN, Ansari MS, Felts AS, Stauffer SR, Emmitte KA, Kessler RM, Niswender CM, Daniels JS, Jones CK, Lindsley CW, Conn PJ. Relationship between in vivo receptor occupancy and efficacy of metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro binding profiles. Neuropsychopharmacology [print-electronic]. 2015 Feb; 40(3): 755-65. PMID: 25241804, PMCID: PMC4289965, PII: npp2014245, DOI: 10.1038/npp.2014.245, ISSN: 1740-634X.

Walker AG, Wenthur CJ, Xiang Z, Rook JM, Emmitte KA, Niswender CM, Lindsley CW, Conn PJ. Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Jan 1/27/2015; 112(4): 1196-201. PMID: 25583490, PMCID: PMC4313856, PII: 1416196112, DOI: 10.1073/pnas.1416196112, ISSN: 1091-6490.

Walker AG, Wenthur CJ, Xiang Z, Rook JM, Emmitte KA, Niswender CM, Lindsley CW, Conn PJ. Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Jan 1/27/2015; 112(4): 1196-201. PMID: 25583490, PMCID: PMC4313856, PII: 1416196112, DOI: 10.1073/pnas.1416196112, ISSN: 1091-6490.

Han C, Chatterjee A, Noetzel MJ, Panarese JD, Smith E, Chase P, Hodder P, Niswender C, Conn PJ, Lindsley CW, Stauffer SR. Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators. Bioorg. Med. Chem. Lett [print-electronic]. 2015 Jan 1/15/2015; 25(2): 384-8. PMID: 25435150, PMCID: PMC4278958, PII: S0960-894X(14)01182-2, DOI: 10.1016/j.bmcl.2014.11.011, ISSN: 1464-3405.

Garcia RC, Dati LM, Torres LH, da Silva MA, Udo MS, Abdalla FM, da Costa JL, Gorjão R, Afeche SC, Yonamine M, Niswender CM, Conn PJ, Camarini R, Sandoval MR, Marcourakis T. M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product. Sci Rep. 2015; 5: 17555. PMID: 26626425, PMCID: PMC4667193, PII: srep17555, DOI: 10.1038/srep17555, ISSN: 2045-2322.

Jalan-Sakrikar N, Field JR, Klar R, Mattmann ME, Gregory KJ, Zamorano R, Engers DW, Bollinger SR, Weaver CD, Days EL, Lewis LM, Utley TJ, Hurtado M, Rigault D, Acher F, Walker AG, Melancon BJ, Wood MR, Lindsley CW, Conn PJ, Xiang Z, Hopkins CR, Niswender CM. Identification of positive allosteric modulators VU0155094 (ML397) and VU0422288 (ML396) reveals new insights into the biology of metabotropic glutamate receptor 7. ACS Chem Neurosci [print-electronic]. 2014 Dec 12/17/2014; 5(12): 1221-37. PMID: 25225882, PMCID: PMC4306484, DOI: 10.1021/cn500153z, ISSN: 1948-7193.

Morris LC, Nance KD, Gentry PR, Days EL, Weaver CD, Niswender CM, Thompson AD, Jones CK, Locuson CW, Morrison RD, Daniels JS, Niswender KD, Lindsley CW. Discovery of (S)-2-cyclopentyl-N-((1-isopropylpyrrolidin2-yl)-9-methyl-1-oxo-2,9-dihydro-1H-pyrrido[3,4-b]indole-4-carboxamide (VU0453379): a novel, CNS penetrant glucagon-like peptide 1 receptor (GLP-1R) positive allosteric modulator (PAM). J. Med. Chem [print-electronic]. 2014 Dec 12/11/2014; 57(23): 10192-7. PMID: 25423411, PMCID: PMC4266362, DOI: 10.1021/jm501375c, ISSN: 1520-4804.

Cho HP, Garcia-Barrantes PM, Brogan JT, Hopkins CR, Niswender CM, Rodriguez AL, Venable DF, Morrison RD, Bubser M, Daniels JS, Jones CK, Conn PJ, Lindsley CW. Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenics. ACS Chem. Biol [print-electronic]. 2014 Oct 10/17/2014; 9(10): 2334-46. PMID: 25137254, PMCID: PMC4201332, DOI: 10.1021/cb500560h, ISSN: 1554-8937.

Cho HP, Garcia-Barrantes PM, Brogan JT, Hopkins CR, Niswender CM, Rodriguez AL, Venable DF, Morrison RD, Bubser M, Daniels JS, Jones CK, Conn PJ, Lindsley CW. Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenics. ACS Chem. Biol [print-electronic]. 2014 Oct 10/17/2014; 9(10): 2334-46. PMID: 25137254, PMCID: PMC4201332, DOI: 10.1021/cb500560h, ISSN: 1554-8937.

Bubser M, Bridges TM, Dencker D, Gould RW, Grannan M, Noetzel MJ, Lamsal A, Niswender CM, Daniels JS, Poslusney MS, Melancon BJ, Tarr JC, Byers FW, Wess J, Duggan ME, Dunlop J, Wood MW, Brandon NJ, Wood MR, Lindsley CW, Conn PJ, Jones CK. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci [print-electronic]. 2014 Oct 10/15/2014; 5(10): 920-42. PMID: 25137629, PMCID: PMC4324418, DOI: 10.1021/cn500128b, ISSN: 1948-7193.

Yin S, Niswender CM. Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indications. Cell. Signal [print-electronic]. 2014 Oct; 26(10): 2284-97. PMID: 24793301, PMCID: PMC4130774, PII: S0898-6568(14)00157-0, DOI: 10.1016/j.cellsig.2014.04.022, ISSN: 1873-3913.

Gentry PR, Kokubo M, Bridges TM, Noetzel MJ, Cho HP, Lamsal A, Smith E, Chase P, Hodder PS, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. 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 [print-electronic]. 2014 Sep 9/25/2014; 57(18): 7804-10. PMID: 25147929, PMCID: PMC4175000, DOI: 10.1021/jm500995y, ISSN: 1520-4804.

Conn PJ, Lindsley CW, Meiler J, Niswender CM. Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders. Nat Rev Drug Discov. 2014 Sep; 13(9): 692-708. PMID: 25176435, PMCID: PMC4208620, PII: nrd4308, DOI: 10.1038/nrd4308, ISSN: 1474-1784.

Bates BS, Rodriguez AL, Felts AS, Morrison RD, Venable DF, Blobaum AL, Byers FW, Lawson KP, Daniels JS, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Emmitte KA. Discovery of VU0431316: a negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. Bioorg. Med. Chem. Lett [print-electronic]. 2014 Aug 8/1/2014; 24(15): 3307-14. PMID: 24969015, PMCID: PMC4090943, PII: S0960-894X(14)00615-5, DOI: 10.1016/j.bmcl.2014.06.003, ISSN: 1464-3405.

Turlington M, Noetzel MJ, Bridges TM, Vinson PN, Steckler T, Lavreysen H, Mackie C, Bartolomé-Nebreda JM, Conde-Ceide S, Tong HM, Macdonald GJ, Daniels JS, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR. Discovery and SAR of a novel series of metabotropic glutamate receptor 5 positive allosteric modulators with high ligand efficiency. Bioorg. Med. Chem. Lett [print-electronic]. 2014 Aug 8/1/2014; 24(15): 3641-6. PMID: 24961642, PMCID: PMC4234308, PII: S0960-894X(14)00444-2, DOI: 10.1016/j.bmcl.2014.04.087, ISSN: 1464-3405.

Gentry PR, Kokubo M, Bridges TM, Cho HP, Smith E, Chase P, Hodder PS, Utley TJ, Rajapakse A, Byers F, Niswender CM, Morrison RD, Daniels JS, Wood MR, Conn PJ, Lindsley CW. Discovery, synthesis and characterization of a highly muscarinic acetylcholine receptor (mAChR)-selective M5-orthosteric antagonist, VU0488130 (ML381): a novel molecular probe. ChemMedChem [print-electronic]. 2014 Aug; 9(8): 1677-82. PMID: 24692176, PMCID: PMC4116439, DOI: 10.1002/cmdc.201402051, ISSN: 1860-7187.

Cho HP, Engers DW, Venable DF, Niswender CM, Lindsley CW, Conn PJ, Emmitte KA, Rodriguez AL. 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 [print-electronic]. 2014 Jul 7/16/2014; 5(7): 597-610. PMID: 24798819, PMCID: PMC4102972, DOI: 10.1021/cn5000343, ISSN: 1948-7193.

Turlington M, Malosh C, Jacobs J, Manka JT, Noetzel MJ, Vinson PN, Jadhav S, Herman EJ, Lavreysen H, Mackie C, Bartolomé-Nebreda JM, Conde-Ceide S, Martín-Martín ML, Tong HM, López S, MacDonald GJ, Steckler T, Daniels JS, Weaver CD, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Stauffer SR. Tetrahydronaphthyridine and dihydronaphthyridinone ethers as positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5). J. Med. Chem [print-electronic]. 2014 Jul 7/10/2014; 57(13): 5620-37. PMID: 24914612, PMCID: PMC4096224, DOI: 10.1021/jm500259z, ISSN: 1520-4804.

Wu H, Wang C, Gregory KJ, Han GW, Cho HP, Xia Y, Niswender CM, Katritch V, Meiler J, Cherezov V, Conn PJ, Stevens RC. Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science [print-electronic]. 2014 Apr 4/4/2014; 344(6179): 58-64. PMID: 24603153, PMCID: PMC3991565, PII: science.1249489, DOI: 10.1126/science.1249489, ISSN: 1095-9203.

Foster DJ, Gentry PR, Lizardi-Ortiz JE, Bridges TM, Wood MR, Niswender CM, Sulzer D, Lindsley CW, Xiang Z, Conn PJ. M5 receptor activation produces opposing physiological outcomes in dopamine neurons depending on the receptor's location. J. Neurosci. 2014 Feb 2/26/2014; 34(9): 3253-62. PMID: 24573284, PMCID: PMC3935086, PII: 34/9/3253, DOI: 10.1523/JNEUROSCI.4896-13.2014, ISSN: 1529-2401.

Sheffler DJ, Nedelovych MT, Williams R, Turner SC, Duerk BB, Robbins MR, Jadhav SB, Niswender CM, Jones CK, Conn PJ, Daniels RN, Lindsley CW. Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: development of a [3.3.0]-based series and other piperidine bioisosteres. Bioorg. Med. Chem. Lett [print-electronic]. 2014 Feb 2/15/2014; 24(4): 1062-6. PMID: 24462664, PMCID: PMC3951244, PII: S0960-894X(14)00030-4, DOI: 10.1016/j.bmcl.2014.01.011, ISSN: 1464-3405.

Jones CK, Sheffler DJ, Williams R, Jadhav SB, Felts AS, Morrison RD, Niswender CM, Daniels JS, Conn PJ, Lindsley CW. Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 1: development of a potent and CNS penetrant [3.1.0]-based lead. Bioorg. Med. Chem. Lett [print-electronic]. 2014 Feb 2/15/2014; 24(4): 1067-70. PMID: 24461352, PMCID: PMC3951249, PII: S0960-894X(14)00032-8, DOI: 10.1016/j.bmcl.2014.01.013, ISSN: 1464-3405.

Yin S, Noetzel MJ, Johnson KA, Zamorano R, Jalan-Sakrikar N, Gregory KJ, Conn PJ, Niswender CM. Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS. J. Neurosci. 2014 Jan 1/1/2014; 34(1): 79-94. PMID: 24381270, PMCID: PMC3866496, PII: 34/1/79, DOI: 10.1523/JNEUROSCI.1129-13.2014, ISSN: 1529-2401.

Blobaum AL, Bridges TM, Byers FW, Turlington ML, Mattmann ME, Morrison RD, Mackie C, Lavreysen H, Bartolomé JM, Macdonald GJ, Steckler T, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR, Daniels JS. 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 [print-electronic]. 2013 Dec; 41(12): 2066-75. PMID: 24003250, PMCID: PMC3834130, PII: dmd.113.052662, DOI: 10.1124/dmd.113.052662, ISSN: 1521-009X.

Gentry PR, Kokubo M, Bridges TM, Kett NR, Harp JM, Cho HP, Smith E, Chase P, Hodder PS, Niswender CM, Daniels JS, Conn PJ, Wood MR, Lindsley CW. 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]isoindol-5(9bH)-one (ML375). J. Med. Chem [print-electronic]. 2013 Nov 11/27/2013; 56(22): 9351-5. PMID: 24164599, PMCID: PMC3876027, DOI: 10.1021/jm4013246, ISSN: 1520-4804.

Felts AS, Rodriguez AL, Morrison RD, Venable DF, Manka JT, Bates BS, Blobaum AL, Byers FW, Daniels JS, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Emmitte KA. Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Nov 11/1/2013; 23(21): 5779-85. PMID: 24074843, PMCID: PMC3846293, PII: S0960-894X(13)01064-0, DOI: 10.1016/j.bmcl.2013.09.001, ISSN: 1464-3405.

Gregory KJ, Herman EJ, Ramsey AJ, Hammond AS, Byun NE, Stauffer SR, Manka JT, Jadhav S, Bridges TM, Weaver CD, Niswender CM, Steckler T, Drinkenburg WH, Ahnaou A, Lavreysen H, Macdonald GJ, Bartolomé JM, Mackie C, Hrupka BJ, Caron MG, Daigle TL, Lindsley CW, Conn PJ, Jones CK. N-aryl piperazine metabotropic glutamate receptor 5 positive allosteric modulators possess efficacy in preclinical models of NMDA hypofunction and cognitive enhancement. J. Pharmacol. Exp. Ther [print-electronic]. 2013 Nov; 347(2): 438-57. PMID: 23965381, PMCID: PMC3807069, PII: jpet.113.206623, DOI: 10.1124/jpet.113.206623, ISSN: 1521-0103.

Turlington M, Noetzel MJ, Chun A, Zhou Y, Gogliotti RD, Nguyen ED, Gregory KJ, Vinson PN, Rook JM, Gogi KK, Xiang Z, Bridges TM, Daniels JS, Jones C, Niswender CM, Meiler J, Conn PJ, Lindsley CW, Stauffer SR. Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): discovery of 5-((3-fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide (ML254). J. Med. Chem [print-electronic]. 2013 Oct 10/24/2013; 56(20): 7976-96. PMID: 24050755, PMCID: PMC3908770, DOI: 10.1021/jm401028t, ISSN: 1520-4804.

Bartolomé-Nebreda JM, Conde-Ceide S, Delgado F, Iturrino L, Pastor J, Pena MÁ, Trabanco AA, Tresadern G, Wassvik CM, Stauffer SR, Jadhav S, Gogi K, Vinson PN, Noetzel MJ, Days E, Weaver CD, Lindsley CW, Niswender CM, Jones CK, Conn PJ, Rombouts F, Lavreysen H, Macdonald GJ, Mackie C, Steckler T. Dihydrothiazolopyridone derivatives as a novel family of positive allosteric modulators of the metabotropic glutamate 5 (mGlu5) receptor. J. Med. Chem [print-electronic]. 2013 Sep 9/26/2013; 56(18): 7243-59. PMID: 23947773, PMCID: PMC3924858, DOI: 10.1021/jm400650w, ISSN: 1520-4804.

Kaufmann K, Romaine I, Days E, Pascual C, Malik A, Yang L, Zou B, Du Y, Sliwoski G, Morrison RD, Denton J, Niswender CM, Daniels JS, Sulikowski GA, Xie XS, Lindsley CW, Weaver CD. ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice. ACS Chem Neurosci [print-electronic]. 2013 Sep 9/18/2013; 4(9): 1278-86. PMID: 23730969, PMCID: PMC3778424, DOI: 10.1021/cn400062a, ISSN: 1948-7193.

Manka JT, Rodriguez AL, Morrison RD, Venable DF, Cho HP, Blobaum AL, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Emmitte KA. Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Sep 9/15/2013; 23(18): 5091-6. PMID: 23932792, PMCID: PMC3901432, PII: S0960-894X(13)00874-3, DOI: 10.1016/j.bmcl.2013.07.029, ISSN: 1464-3405.

Bridges TM, Rook JM, Noetzel MJ, Morrison RD, Zhou Y, Gogliotti RD, Vinson PN, Xiang Z, Jones CK, Niswender CM, Lindsley CW, Stauffer SR, Conn PJ, Daniels JS. 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 [print-electronic]. 2013 Sep; 41(9): 1703-14. PMID: 23821185, PMCID: PMC3876804, PII: dmd.113.052084, DOI: 10.1124/dmd.113.052084, ISSN: 1521-009X.

Amato RJ, Felts AS, Rodriguez AL, Venable DF, Morrison RD, Byers FW, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Jones CK, Emmitte KA. 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 [print-electronic]. 2013 Aug 8/21/2013; 4(8): 1217-28. PMID: 23682684, PMCID: PMC3750677, DOI: 10.1021/cn400070k, ISSN: 1948-7193.

Lovell KM, Felts AS, Rodriguez AL, Venable DF, Cho HP, Morrison RD, Byers FW, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Emmitte KA. N-Acyl-N'-arylpiperazines as negative allosteric modulators of mGlu1: identification of VU0469650, a potent and selective tool compound with CNS exposure in rats. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Jul 7/1/2013; 23(13): 3713-8. PMID: 23727046, PMCID: PMC3875306, PII: S0960-894X(13)00606-9, DOI: 10.1016/j.bmcl.2013.05.020, ISSN: 1464-3405.

Gentry PR, Bridges TM, Lamsal A, Vinson PN, Smith E, Chase P, Hodder PS, Engers JL, Niswender CM, Daniels JS, Conn PJ, Wood MR, Lindsley CW. Discovery of ML326: The first sub-micromolar, selective M5 PAM. Bioorg. Med. Chem. Lett [print-electronic]. 2013 May 5/15/2013; 23(10): 2996-3000. PMID: 23562060, PMCID: PMC3634896, PII: S0960-894X(13)00348-X, DOI: 10.1016/j.bmcl.2013.03.032, ISSN: 1464-3405.

Noetzel MJ, Gregory KJ, Vinson PN, Manka JT, Stauffer SR, Lindsley CW, Niswender CM, Xiang Z, Conn PJ. A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling. Mol. Pharmacol [print-electronic]. 2013 Apr; 83(4): 835-47. PMID: 23348500, PMCID: PMC3608436, PII: mol.112.082891, DOI: 10.1124/mol.112.082891, ISSN: 1521-0111.

Poslusney MS, Melancon BJ, Gentry PR, Sheffler DJ, Bridges TM, Utley TJ, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Wood MR. Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Mar 3/15/2013; 23(6): 1860-4. PMID: 23416001, PMCID: PMC3594472, PII: S0960-894X(13)00039-5, DOI: 10.1016/j.bmcl.2013.01.017, ISSN: 1464-3405.

Rook JM, Noetzel MJ, Pouliot WA, Bridges TM, Vinson PN, Cho HP, Zhou Y, Gogliotti RD, Manka JT, Gregory KJ, Stauffer SR, Dudek FE, Xiang Z, Niswender CM, Daniels JS, Jones CK, Lindsley CW, Conn PJ. Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol. Psychiatry [print-electronic]. 2013 Mar 3/15/2013; 73(6): 501-9. PMID: 23140665, PMCID: PMC3572342, PII: S0006-3223(12)00806-2, DOI: 10.1016/j.biopsych.2012.09.012, ISSN: 1873-2402.

Johnson KA, Jones CK, Tantawy MN, Bubser M, Marvanova M, Ansari MS, Baldwin RM, Conn PJ, Niswender CM. The metabotropic glutamate receptor 8 agonist (S)-3,4-DCPG reverses motor deficits in prolonged but not acute models of Parkinson's disease. Neuropharmacology [print-electronic]. 2013 Mar; 66: 187-95. PMID: 22546615, PMCID: PMC3432150, PII: S0028-3908(12)00144-X, DOI: 10.1016/j.neuropharm.2012.03.029, ISSN: 1873-7064.

Yin S, Zamorano R, Conn PJ, Niswender CM. Functional selectivity induced by mGlu4 receptor positive allosteric modulation and concomitant activation of Gq coupled receptors. Neuropharmacology [print-electronic]. 2013 Mar; 66: 122-32. PMID: 22426233, PMCID: PMC3412075, PII: S0028-3908(12)00087-1, DOI: 10.1016/j.neuropharm.2012.03.003, ISSN: 1873-7064.

Melancon BJ, Poslusney MS, Gentry PR, Tarr JC, Sheffler DJ, Mattmann ME, Bridges TM, Utley TJ, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Wood MR. Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Jan 1/15/2013; 23(2): 412-6. PMID: 23237839, PMCID: PMC3534865, PII: S0960-894X(12)01544-2, DOI: 10.1016/j.bmcl.2012.11.092, ISSN: 1464-3405.

Gregory KJ, Noetzel MJ, Niswender CM. Pharmacology of metabotropic glutamate receptor allosteric modulators: structural basis and therapeutic potential for CNS disorders. Prog Mol Biol Transl Sci. 2013; 115: 61-121. PMID: 23415092, PII: B978-0-12-394587-7.00002-6, DOI: 10.1016/B978-0-12-394587-7.00002-6, ISSN: 1878-0814.

Klein MT, Vinson PN, Niswender CM. Approaches for probing allosteric interactions at 7 transmembrane spanning receptors. Prog Mol Biol Transl Sci. 2013; 115: 1-59. PMID: 23415091, PII: B978-0-12-394587-7.00001-4, DOI: 10.1016/B978-0-12-394587-7.00001-4, ISSN: 1878-0814.

Sheffler DJ, Sevel C, Le U, Lovell KM, Tarr JC, Carrington SJ, Cho HP, Digby GJ, Niswender CM, Conn PJ, Hopkins CR, Wood MR, Lindsley CW. Further exploration of M1 allosteric agonists: subtle structural changes abolish M1 allosteric agonism and result in pan-mAChR orthosteric antagonism. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Jan 1/1/2013; 23(1): 223-7. PMID: 23200253, PMCID: PMC3525729, PII: S0960-894X(12)01434-5, DOI: 10.1016/j.bmcl.2012.10.132, ISSN: 1464-3405.

Le U, Melancon BJ, Bridges TM, Vinson PN, Utley TJ, Lamsal A, Rodriguez AL, Venable D, Sheffler DJ, Jones CK, Blobaum AL, Wood MR, Daniels JS, Conn PJ, Niswender CM, Lindsley CW, Hopkins CR. Discovery of a selective M4 positive allosteric modulator based on the 3-amino-thieno[2,3-b]pyridine-2-carboxamide scaffold: development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia. Bioorg. Med. Chem. Lett [print-electronic]. 2013 Jan 1/1/2013; 23(1): 346-50. PMID: 23177787, PMCID: PMC3535830, PII: S0960-894X(12)01364-9, DOI: 10.1016/j.bmcl.2012.10.073, ISSN: 1464-3405.

Digby GJ, Utley TJ, Lamsal A, Sevel C, Sheffler DJ, Lebois EP, Bridges TM, Wood MR, Niswender CM, Lindsley CW, Conn PJ. Chemical modification of the M(1) agonist VU0364572 reveals molecular switches in pharmacology and a bitopic binding mode. ACS Chem Neurosci [print-electronic]. 2012 Dec 12/19/2012; 3(12): 1025-36. PMID: 23259038, PMCID: PMC3526969, DOI: 10.1021/cn300103e, ISSN: 1948-7193.

Rodriguez AL, Zhou Y, Williams R, Weaver CD, Vinson PN, Dawson ES, Steckler T, Lavreysen H, Mackie C, Bartolomé JM, Macdonald GJ, Daniels JS, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Stauffer SR. Discovery and SAR of a novel series of non-MPEP site mGlu5 PAMs based on an aryl glycine sulfonamide scaffold. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Dec 12/15/2012; 22(24): 7388-92. PMID: 23142615, PMCID: PMC3539767, PII: S0960-894X(12)01359-5, DOI: 10.1016/j.bmcl.2012.10.068, ISSN: 1464-3405.

Tarr JC, Turlington ML, Reid PR, Utley TJ, Sheffler DJ, Cho HP, Klar R, Pancani T, Klein MT, Bridges TM, Morrison RD, Blobaum AL, Xiang Z, Daniels JS, Niswender CM, Conn PJ, Wood MR, Lindsley CW. Targeting selective activation of M(1) for the treatment of Alzheimer's disease: further chemical optimization and pharmacological characterization of the M(1) positive allosteric modulator ML169. ACS Chem Neurosci [print-electronic]. 2012 Nov 11/21/2012; 3(11): 884-95. PMID: 23173069, PMCID: PMC3503349, DOI: 10.1021/cn300068s, ISSN: 1948-7193.

Poslusney MS, Sevel C, Utley TJ, Bridges TM, Morrison RD, Kett NR, Sheffler DJ, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. Synthesis and biological characterization of a series of novel diaryl amide M1 antagonists. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Nov 11/15/2012; 22(22): 6923-8. PMID: 23062550, PMCID: PMC3897205, PII: S0960-894X(12)01155-9, DOI: 10.1016/j.bmcl.2012.09.011, ISSN: 1464-3405.

Gregory KJ, Noetzel MJ, Rook JM, Vinson PN, Stauffer SR, Rodriguez AL, Emmitte KA, Zhou Y, Chun AC, Felts AS, Chauder BA, Lindsley CW, Niswender CM, Conn PJ. Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships. Mol. Pharmacol [print-electronic]. 2012 Nov; 82(5): 860-75. PMID: 22863693, PMCID: PMC3477233, PII: mol.112.080531, DOI: 10.1124/mol.112.080531, ISSN: 1521-0111.

Manka JT, Vinson PN, Gregory KJ, Zhou Y, Williams R, Gogi K, Days E, Jadhav S, Herman EJ, Lavreysen H, Mackie C, Bartolomé JM, Macdonald GJ, Steckler T, Daniels JS, Weaver CD, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Stauffer SR. Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Oct 10/15/2012; 22(20): 6481-5. PMID: 22981332, PMCID: PMC3755010, PII: S0960-894X(12)01043-8, DOI: 10.1016/j.bmcl.2012.08.043, ISSN: 1464-3405.

Morrison RD, Blobaum AL, Byers FW, Santomango TS, Bridges TM, Stec D, Brewer KA, Sanchez-Ponce R, Corlew MM, Rush R, Felts AS, Manka J, Bates BS, Venable DF, Rodriguez AL, Jones CK, Niswender CM, Conn PJ, Lindsley CW, Emmitte KA, Daniels JS. The role of aldehyde oxidase and xanthine oxidase in the biotransformation of a novel negative allosteric modulator of metabotropic glutamate receptor subtype 5. Drug Metab. Dispos [print-electronic]. 2012 Sep; 40(9): 1834-45. PMID: 22711749, PMCID: PMC3422546, PII: dmd.112.046136, DOI: 10.1124/dmd.112.046136, ISSN: 1521-009X.

Mueller R, Dawson ES, Niswender CM, Butkiewicz M, Hopkins CR, Weaver CD, Lindsley CW, Conn PJ, Meiler J. Iterative experimental and virtual high-throughput screening identifies metabotropic glutamate receptor subtype 4 positive allosteric modulators. J Mol Model [print-electronic]. 2012 Sep; 18(9): 4437-46. PMID: 22592386, PMCID: PMC3766737, DOI: 10.1007/s00894-012-1441-0, ISSN: 0948-5023.

Melancon BJ, Utley TJ, Sevel C, Mattmann ME, Cheung YY, Bridges TM, Morrison RD, Sheffler DJ, Niswender CM, Daniels JS, Conn PJ, Lindsley CW, Wood MR. Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Aug 8/1/2012; 22(15): 5035-40. PMID: 22749871, PMCID: PMC3883446, PII: S0960-894X(12)00765-2, DOI: 10.1016/j.bmcl.2012.06.018, ISSN: 1464-3405.

Salovich JM, Vinson PN, Sheffler DJ, Lamsal A, Utley TJ, Blobaum AL, Bridges TM, Le U, Jones CK, Wood MR, Daniels JS, Conn PJ, Niswender CM, Lindsley CW, Hopkins CR. Discovery of N-(4-methoxy-7-methylbenzo[d]thiazol-2-yl)isonicatinamide, ML293, as a novel, selective and brain penetrant positive allosteric modulator of the muscarinic 4 (M4) receptor. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Aug 8/1/2012; 22(15): 5084-8. PMID: 22738637, PMCID: PMC3401285, PII: S0960-894X(12)00721-4, DOI: 10.1016/j.bmcl.2012.05.109, ISSN: 1464-3405.

Digby GJ, Noetzel MJ, Bubser M, Utley TJ, Walker AG, Byun NE, Lebois EP, Xiang Z, Sheffler DJ, Cho HP, Davis AA, Nemirovsky NE, Mennenga SE, Camp BW, Bimonte-Nelson HA, Bode J, Italiano K, Morrison R, Daniels JS, Niswender CM, Olive MF, Lindsley CW, Jones CK, Conn PJ. Novel allosteric agonists of M1 muscarinic acetylcholine receptors induce brain region-specific responses that correspond with behavioral effects in animal models. J. Neurosci. 2012 Jun 6/20/2012; 32(25): 8532-44. PMID: 22723693, PMCID: PMC3398407, PII: 32/25/8532, DOI: 10.1523/JNEUROSCI.0337-12.2012, ISSN: 1529-2401.

Sheffler DJ, Wenthur CJ, Bruner JA, Carrington SJ, Vinson PN, Gogi KK, Blobaum AL, Morrison RD, Vamos M, Cosford ND, Stauffer SR, Daniels JS, Niswender CM, Conn PJ, Lindsley CW. Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu5 PAM. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Jun 6/15/2012; 22(12): 3921-5. PMID: 22607673, PMCID: PMC3365510, PII: S0960-894X(12)00562-8, DOI: 10.1016/j.bmcl.2012.04.112, ISSN: 1464-3405.

Melancon BJ, Gogliotti RD, Tarr JC, Saleh SA, Chauder BA, Lebois EP, Cho HP, Utley TJ, Sheffler DJ, Bridges TM, Morrison RD, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Wood MR. Continued optimization of the MLPCN probe ML071 into highly potent agonists of the hM1 muscarinic acetylcholine receptor. Bioorg. Med. Chem. Lett [print-electronic]. 2012 May 5/15/2012; 22(10): 3467-72. PMID: 22507963, PMCID: PMC3348459, PII: S0960-894X(12)00409-X, DOI: 10.1016/j.bmcl.2012.03.088, ISSN: 1464-3405.

Mueller R, Dawson ES, Meiler J, Rodriguez AL, Chauder BA, Bates BS, Felts AS, Lamb JP, Menon UN, Jadhav SB, Kane AS, Jones CK, Gregory KJ, Niswender CM, Conn PJ, Olsen CM, Winder DG, Emmitte KA, Lindsley CW. Discovery of 2-(2-benzoxazoyl amino)-4-aryl-5-cyanopyrimidine as negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu5): from an artificial neural network virtual screen to an in vivo tool compound. ChemMedChem [print-electronic]. 2012 Mar 3/5/2012; 7(3): 406-14. PMID: 22267125, PMCID: PMC3517057, DOI: 10.1002/cmdc.201100510, ISSN: 1860-7187.

Melancon BJ, Hopkins CR, Wood MR, Emmitte KA, Niswender CM, Christopoulos A, Conn PJ, Lindsley CW. Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery. J. Med. Chem [print-electronic]. 2012 Feb 2/23/2012; 55(4): 1445-64. PMID: 22148748, PMCID: PMC3349997, DOI: 10.1021/jm201139r, ISSN: 1520-4804.

Jones CK, Bubser M, Thompson AD, Dickerson JW, Turle-Lorenzo N, Amalric M, Blobaum AL, Bridges TM, Morrison RD, Jadhav S, Engers DW, Italiano K, Bode J, Daniels JS, Lindsley CW, Hopkins CR, Conn PJ, Niswender CM. 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. J. Pharmacol. Exp. Ther [print-electronic]. 2012 Feb; 340(2): 404-21. PMID: 22088953, PMCID: PMC3263969, PII: jpet.111.187443, DOI: 10.1124/jpet.111.187443, ISSN: 1521-0103.

Noetzel MJ, Rook JM, Vinson PN, Cho HP, Days E, Zhou Y, Rodriguez AL, Lavreysen H, Stauffer SR, Niswender CM, Xiang Z, Daniels JS, Jones CK, Lindsley CW, Weaver CD, Conn PJ. Functional impact of allosteric agonist activity of selective positive allosteric modulators of metabotropic glutamate receptor subtype 5 in regulating central nervous system function. Mol. Pharmacol [print-electronic]. 2012 Feb; 81(2): 120-33. PMID: 22021324, PMCID: PMC3263948, PII: mol.111.075184, DOI: 10.1124/mol.111.075184, ISSN: 1521-0111.

Melancon BJ, Lamers AP, Bridges TM, Sulikowski GA, Utley TJ, Sheffler DJ, Noetzel MJ, Morrison RD, Daniels JS, Niswender CM, Jones CK, Conn PJ, Lindsley CW, Wood MR. Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012. Bioorg. Med. Chem. Lett [print-electronic]. 2012 Jan 1/15/2012; 22(2): 1044-8. PMID: 22197142, PMCID: PMC3434972, PII: S0960-894X(11)01654-4, DOI: 10.1016/j.bmcl.2011.11.110, ISSN: 1464-3405.

Utley T, Haddenham D, Salovich JM, Zamorano R, Vinson PN, Lindsley CW, Hopkins CR, Niswender CM. Synthesis and SAR of a novel metabotropic glutamate receptor 4 (mGlu4) antagonist: unexpected 'molecular switch' from a closely related mGlu4 positive allosteric modulator. Bioorg. Med. Chem. Lett [print-electronic]. 2011 Dec 12/1/2011; 21(23): 6955-9. PMID: 22030026, PMCID: PMC3319082, PII: S0960-894X(11)01386-2, DOI: 10.1016/j.bmcl.2011.09.131, ISSN: 1464-3405.

Jones CK, Engers DW, Thompson AD, Field JR, Blobaum AL, Lindsley SR, Zhou Y, Gogliotti RD, Jadhav S, Zamorano R, Bogenpohl J, Smith Y, Morrison R, Daniels JS, Weaver CD, Conn PJ, Lindsley CW, Niswender CM, Hopkins CR. Discovery, synthesis, and structure-activity relationship development of a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): characterization of a novel positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu(4)) with oral efficacy in an antiparkinsonian animal model. J. Med. Chem [print-electronic]. 2011 Nov 11/10/2011; 54(21): 7639-47. PMID: 21966889, PMCID: PMC3226828, DOI: 10.1021/jm200956q, ISSN: 1520-4804.

Johnson KA, Niswender CM, Conn PJ, Xiang Z. Activation of group II metabotropic glutamate receptors induces long-term depression of excitatory synaptic transmission in the substantia nigra pars reticulata. Neurosci. Lett [print-electronic]. 2011 Oct 10/24/2011; 504(2): 102-6. PMID: 21945652, PMCID: PMC3556513, PII: S0304-3940(11)01272-9, DOI: 10.1016/j.neulet.2011.09.007, ISSN: 1872-7972.

Reid PR, Bridges TM, Sheffler DJ, Cho HP, Lewis LM, Days E, Daniels JS, Jones CK, Niswender CM, Weaver CD, Conn PJ, Lindsley CW, Wood MR. Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): the development of ML169, an MLPCN probe. Bioorg. Med. Chem. Lett [print-electronic]. 2011 May 5/1/2011; 21(9): 2697-701. PMID: 21194936, PMCID: PMC3082000, PII: S0960-894X(10)01769-5, DOI: 10.1016/j.bmcl.2010.12.015, ISSN: 1464-3405.

Lamb JP, Engers DW, Niswender CM, Rodriguez AL, Venable DF, Conn PJ, Lindsley CW. Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists. Bioorg. Med. Chem. Lett [print-electronic]. 2011 May 5/1/2011; 21(9): 2711-4. PMID: 21183344, PMCID: PMC3179182, PII: S0960-894X(10)01744-0, DOI: 10.1016/j.bmcl.2010.11.119, ISSN: 1464-3405.

Cheung YY, Zamorano R, Blobaum AL, Weaver CD, Conn PJ, Lindsley CW, Niswender CM, Hopkins CR. Solution-phase parallel synthesis and SAR of homopiperazinyl analogs as positive allosteric modulators of mGlu4. ACS Comb Sci [print-electronic]. 2011 Mar 3/14/2011; 13(2): 159-65. PMID: 21338051, PMCID: PMC3057427, DOI: 10.1021/co1000508, ISSN: 2156-8944.

Williams R, Manka JT, Rodriguez AL, Vinson PN, Niswender CM, Weaver CD, Jones CK, Conn PJ, Lindsley CW, Stauffer SR. Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold. Bioorg. Med. Chem. Lett [print-electronic]. 2011 Mar 3/1/2011; 21(5): 1350-3. PMID: 21315585, PMCID: PMC3498823, PII: S0960-894X(11)00067-9, DOI: 10.1016/j.bmcl.2011.01.044, ISSN: 1464-3405.

Engers DW, Field JR, Le U, Zhou Y, Bolinger JD, Zamorano R, Blobaum AL, Jones CK, Jadhav S, Weaver CD, Conn PJ, Lindsley CW, Niswender CM, Hopkins CR. 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 [print-electronic]. 2011 Feb 2/24/2011; 54(4): 1106-10. PMID: 21247167, PMCID: PMC3166797, DOI: 10.1021/jm101271s, ISSN: 1520-4804.

Willis BS, Niswender CM, Su T, Amieux PS, McKnight GS. Cell-type specific expression of a dominant negative PKA mutation in mice. PLoS ONE. 2011; 6(4): e18772. PMID: 21533282, PMCID: PMC3075275, DOI: 10.1371/journal.pone.0018772, ISSN: 1932-6203.

Rodriguez AL, Grier MD, Jones CK, Herman EJ, Kane AS, Smith RL, Williams R, Zhou Y, Marlo JE, Days EL, Blatt TN, Jadhav S, Menon UN, Vinson PN, Rook JM, Stauffer SR, Niswender CM, Lindsley CW, Weaver CD, Conn PJ. 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. Mol. Pharmacol [print-electronic]. 2010 Dec; 78(6): 1105-23. PMID: 20923853, PMCID: PMC2993468, PII: mol.110.067207, DOI: 10.1124/mol.110.067207, ISSN: 1521-0111.

Engers DW, Gentry PR, Williams R, Bolinger JD, Weaver CD, Menon UN, Conn PJ, Lindsley CW, Niswender CM, Hopkins CR. Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS). Bioorg. Med. Chem. Lett [print-electronic]. 2010 Sep 9/1/2010; 20(17): 5175-8. PMID: 20667732, PMCID: PMC2922490, PII: S0960-894X(10)00951-0, DOI: 10.1016/j.bmcl.2010.07.007, ISSN: 1464-3405.

Williams R, Zhou Y, Niswender CM, Luo Q, Conn PJ, Lindsley CW, Hopkins CR. Re-exploration of the PHCCC Scaffold: Discovery of Improved Positive Allosteric Modulators of mGluR4. ACS Chem Neurosci. 2010 Jun 6/16/2010; 1(6): 411-9. PMID: 20582156, PMCID: PMC2889702, DOI: 10.1021/cn9000318, ISSN: 1948-7193.

Niswender CM, Johnson KA, Miller NR, Ayala JE, Luo Q, Williams R, Saleh S, Orton D, Weaver CD, Conn PJ. Context-dependent pharmacology exhibited by negative allosteric modulators of metabotropic glutamate receptor 7. Mol. Pharmacol [print-electronic]. 2010 Mar; 77(3): 459-68. PMID: 20026717, PMCID: PMC2835423, PII: mol.109.058768, DOI: 10.1124/mol.109.058768, ISSN: 1521-0111.

Niswender CM, Conn PJ. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu. Rev. Pharmacol. Toxicol. 2010; 50: 295-322. PMID: 20055706, PMCID: PMC2904507, DOI: 10.1146/annurev.pharmtox.011008.145533, ISSN: 1545-4304.

Lebois EP, Bridges TM, Lewis LM, Dawson ES, Kane AS, Xiang Z, Jadhav SB, Yin H, Kennedy JP, Meiler J, Niswender CM, Jones CK, Conn PJ, Weaver CD, Lindsley CW. Discovery and characterization of novel subtype-selective allosteric agonists for the investigation of M(1) receptor function in the central nervous system. ACS Chem Neurosci. 2010; 1(2): 104-21. PMID: 21961051, PMCID: PMC3180826, DOI: 10.1021/cn900003h, ISSN: 1948-7193.

Johnson KA, Conn PJ, Niswender CM. Glutamate receptors as therapeutic targets for Parkinson's disease. CNS Neurol Disord Drug Targets. 2009 Dec; 8(6): 475-91. PMID: 19702565, PMCID: PMC3005251, PII: 5, ISSN: 1996-3181.

Williams R, Johnson KA, Gentry PR, Niswender CM, Weaver CD, Conn PJ, Lindsley CW, Hopkins CR. Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4). Bioorg. Med. Chem. Lett [print-electronic]. 2009 Sep 9/1/2009; 19(17): 4967-70. PMID: 19640716, PMCID: PMC2752865, PII: S0960-894X(09)01033-6, DOI: 10.1016/j.bmcl.2009.07.072, ISSN: 1464-3405.

Sheffler DJ, Williams R, Bridges TM, Xiang Z, Kane AS, Byun NE, Jadhav S, Mock MM, Zheng F, Lewis LM, Jones CK, Niswender CM, Weaver CD, Lindsley CW, Conn PJ. A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning. Mol. Pharmacol [print-electronic]. 2009 Aug; 76(2): 356-68. PMID: 19407080, PMCID: PMC2713127, PII: mol.109.056531, DOI: 10.1124/mol.109.056531, ISSN: 1521-0111.

Engers DW, Niswender CM, Weaver CD, Jadhav S, Menon UN, Zamorano R, Conn PJ, Lindsley CW, Hopkins CR. Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs). J. Med. Chem. 2009 Jul 7/23/2009; 52(14): 4115-8. PMID: 19469556, PMCID: PMC2765192, DOI: 10.1021/jm9005065, ISSN: 1520-4804.

Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW. 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. 2009 Jun 6/11/2009; 52(11): 3445-8. PMID: 19438238, PMCID: PMC3875304, DOI: 10.1021/jm900286j, ISSN: 1520-4804.

Hopkins CR, Lindsley CW, Niswender CM. MGluR4-positive allosteric modulation as potential treatment for Parkinson's disease. Future Med Chem. 2009 Jun; 1(3): 501-13. PMID: 20161443, PMCID: PMC2790174, DOI: 10.4155/fmc.09.38, ISSN: 1756-8927.

Marlo JE, Niswender CM, Days EL, Bridges TM, Xiang Y, Rodriguez AL, Shirey JK, Brady AE, Nalywajko T, Luo Q, Austin CA, Williams MB, Kim K, Williams R, Orton D, Brown HA, Lindsley CW, Weaver CD, Conn PJ. Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol. Pharmacol [print-electronic]. 2009 Mar; 75(3): 577-88. PMID: 19047481, PMCID: PMC2684909, PII: mol.108.052886, DOI: 10.1124/mol.108.052886, ISSN: 1521-0111.

Williams R, Niswender CM, Luo Q, Le U, Conn PJ, Lindsley CW. Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead. Bioorg. Med. Chem. Lett [print-electronic]. 2009 Feb 2/1/2009; 19(3): 962-6. PMID: 19097893, PMCID: PMC3787871, PII: S0960-894X(08)01468-6, DOI: 10.1016/j.bmcl.2008.11.104, ISSN: 1464-3405.

Aldrich LN, Lebois EP, Lewis LM, Nalywajko NT, Niswender CM, Weaver CD, Conn PJ, Lindsley CW. MAOS ls for the general synthesis and lead optimization of 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines. Tetrahedron Lett. 2009 Jan 1/14/2009; 50(2): 212-5. PMID: 22090663, PMCID: PMC3214729, DOI: 10.1016/j.tetlet.2008.10.127, ISSN: 0040-4039.

Weaver CD, Sheffler DJ, Lewis LM, Bridges TM, Williams R, Nalywajko NT, Kennedy JP, Mulder MM, Jadhav S, Aldrich LA, Jones CK, Marlo JE, Niswender CM, Mock MM, Zheng F, Conn PJ, Lindsley CW. Discovery and development of a potent and highly selective small molecule muscarinic acetylcholine receptor subtype I (mAChR 1 or M1) antagonist in vitro and in vivo probe. Curr Top Med Chem. 2009; 9(13): 1217-26. PMID: 19807667, PII: CTMC-Abs-011-9-13, ISSN: 1873-4294.

Lindsley CW, Niswender CM, Engers DW, Hopkins CR. Recent progress in the development of mGluR4 positive allosteric modulators for the treatment of Parkinson's disease. Curr Top Med Chem. 2009; 9(10): 949-63. PMID: 19754407, ISSN: 1873-4294.

Niswender CM, Johnson KA, Weaver CD, Jones CK, Xiang Z, Luo Q, Rodriguez AL, Marlo JE, de Paulis T, Thompson AD, Days EL, Nalywajko T, Austin CA, Williams MB, Ayala JE, Williams R, Lindsley CW, Conn PJ. Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4. Mol. Pharmacol [print-electronic]. 2008 Nov; 74(5): 1345-58. PMID: 18664603, PMCID: PMC2574552, PII: mol.108.049551, DOI: 10.1124/mol.108.049551, ISSN: 1521-0111.

Niswender CM, Lebois EP, Luo Q, Kim K, Muchalski H, Yin H, Conn PJ, Lindsley CW. 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. Bioorg. Med. Chem. Lett [print-electronic]. 2008 Oct 10/15/2008; 18(20): 5626-30. PMID: 18793851, PMCID: PMC3182458, PII: S0960-894X(08)01018-4, DOI: 10.1016/j.bmcl.2008.08.087, ISSN: 1464-3405.

Ayala JE, Niswender CM, Luo Q, Banko JL, Conn PJ. Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated. Neuropharmacology [print-electronic]. 2008 Apr; 54(5): 804-14. PMID: 18255102, PMCID: PMC2431171, PII: S0028-3908(07)00397-8, DOI: 10.1016/j.neuropharm.2007.12.009, ISSN: 0028-3908.

Niswender CM, Johnson KA, Luo Q, Ayala JE, Kim C, Conn PJ, Weaver CD. 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. Mol. Pharmacol [print-electronic]. 2008 Apr; 73(4): 1213-24. PMID: 18171729, PII: mol.107.041053, DOI: 10.1124/mol.107.041053, ISSN: 1521-0111.

Lewis LM, Sheffler D, Williams R, Bridges TM, Kennedy JP, Brogan JT, Mulder MJ, Williams L, Nalywajko NT, Niswender CM, Weaver CD, Conn PJ, Lindsley CW. Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists. Bioorg. Med. Chem. Lett [print-electronic]. 2008 Feb 2/1/2008; 18(3): 885-90. PMID: 18178088, PMCID: PMC2275053, PII: S0960-894X(07)01510-7, DOI: 10.1016/j.bmcl.2007.12.051, ISSN: 1464-3405.

Shirey JK, Xiang Z, Orton D, Brady AE, Johnson KA, Williams R, Ayala JE, Rodriguez AL, Wess J, Weaver D, Niswender CM, Conn PJ. An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission. Nat. Chem. Biol [print-electronic]. 2008 Jan; 4(1): 42-50. PMID: 18059262, PII: nchembio.2007.55, DOI: 10.1038/nchembio.2007.55, ISSN: 1552-4469.

Hemstapat K, Da Costa H, Nong Y, Brady AE, Luo Q, Niswender CM, Tamagnan GD, Conn PJ. A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors. J. Pharmacol. Exp. Ther [print-electronic]. 2007 Jul; 322(1): 254-64. PMID: 17416742, PII: jpet.106.117093, DOI: 10.1124/jpet.106.117093, ISSN: 0022-3565.

Conn PJ, Niswender CM. MGluR7's lucky number. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2006 Jan 1/10/2006; 103(2): 251-2. PMID: 16407154, PMCID: PMC1326193, PII: 0510051103, DOI: 10.1073/pnas.0510051103, ISSN: 0027-8424.

Niswender CM, Willis BS, Wallen A, Sweet IR, Jetton TL, Thompson BR, Wu C, Lange AJ, McKnight GS. Cre recombinase-dependent expression of a constitutively active mutant allele of the catalytic subunit of protein kinase A. Genesis. 2005 Nov; 43(3): 109-19. PMID: 16155866, DOI: 10.1002/gene.20159, ISSN: 1526-954X.

Niswender CM, Jones CK, Conn PJ. New therapeutic frontiers for metabotropic glutamate receptors. Curr Top Med Chem. 2005; 5(9): 847-57. PMID: 16178730, ISSN: 1568-0266.

Niswender CM, McKnight GS. Transgenic models for the study of cAMP signaling. Transgenic Models in Pharmacology. 2004; 159((Handbook of Experimental Pharmacology)): 131-64.

Niswender CM, Ishihara RW, Judge LM, Zhang C, Shokat KM, McKnight GS. Protein engineering of protein kinase A catalytic subunits results in the acquisition of novel inhibitor sensitivity. J. Biol. Chem [print-electronic]. 2002 Aug 8/9/2002; 277(32): 28916-22. PMID: 12034735, PII: M203327200, DOI: 10.1074/jbc.M203327200, ISSN: 0021-9258.

Niswender CM. Strategies and requirements for the detection of RNA editing in G protein coupled-receptor RNA. Meth. Enzymol. 2002; 343: 476-92. PMID: 11665586, ISSN: 0076-6879.

Berg KA, Cropper JD, Niswender CM, Sanders-Bush E, Emeson RB, Clarke WP. RNA-editing of the 5-HT(2C) receptor alters agonist-receptor-effector coupling specificity. Br. J. Pharmacol. 2001 Sep; 134(2): 386-92. PMID: 11564657, PMCID: PMC1572953, DOI: 10.1038/sj.bjp.0704255, ISSN: 0007-1188.

Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E. RNA editing of the human serotonin 5-HT2C receptor. alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharmacology. 2001 May; 24(5): 478-91. PMID: 11282248, PII: S0893-133X(00)00223-2, DOI: 10.1016/S0893-133X(00)00223-2, ISSN: 0893-133X.

Herrick-Davis K, Grinde E, Niswender CM. Serotonin 5-HT2C receptor RNA editing alters receptor basal activity: implications for serotonergic signal transduction. J. Neurochem. 1999 Oct; 73(4): 1711-7. PMID: 10501219, ISSN: 0022-3042.

Backstrom JR, Chang MS, Chu H, Niswender CM, Sanders-Bush E. Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD). Neuropsychopharmacology. 1999 Aug; 21(2 Suppl): 77S-81S. PMID: 10432492, PII: S0893133X99000056, DOI: 10.1016/S0893-133X(99)00005-6, ISSN: 0893-133X.

Niswender CM, Copeland SC, Herrick-Davis K, Emeson RB, Sanders-Bush E. RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J. Biol. Chem. 1999 Apr 4/2/1999; 274(14): 9472-8. PMID: 10092629, ISSN: 0021-9258.

Niswender CM, Sanders-Bush E, Emeson RB. Identification and characterization of RNA editing events within the 5-HT2C receptor. Ann. N. Y. Acad. Sci. 1998 Dec 12/15/1998; 861: 38-48. PMID: 9928237, ISSN: 0077-8923.

Niswender CM. Recent advances in mammalian RNA editing. Cell. Mol. Life Sci. 1998 Sep; 54(9): 946-64. PMID: 9791538, ISSN: 1420-682X.

Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders-Bush E, Emeson RB. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature. 1997 May 5/15/1997; 387(6630): 303-8. PMID: 9153397, DOI: 10.1038/387303a0, ISSN: 0028-0836.

Rueter SM, Burns CM, Coode SA, Mookherjee P, Emeson RB. Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine. Science. 1995 Mar 3/10/1995; 267(5203): 1491-4. PMID: 7878468, ISSN: 0036-8075.

Hagley MT, Hulisz DT, Burns CM. Hepatotoxicity associated with angiotensin-converting enzyme inhibitors. Ann Pharmacother. 1993 Feb; 27(2): 228-31. PMID: 8292107, ISSN: 1060-0280.

Available Postdoctoral Position Details
Posted: 3/15/2018

Vanderbilt University Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery

Post-Doctoral Fellow

The Niswender lab is seeking an inquisitive and motivated postdoctoral fellow to join our Neurodevelopmental Disorders group within the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD). Students and postdocs within the VCNDD receive exposure to all facets of academic drug discovery, ranging from testing basic science hypotheses, compound development, and translational neuroscience. Our group integrates elements of neuroscience, behavioral and molecular pharmacology, drug metabolism and pharmacokinetics, and electrophysiology to interrogate the role of metabotropic glutamate receptors and muscarinic acetylcholine receptors in autism and autism-associated disorders. The candidate will work with Dr. Colleen Niswender and several other senior scientists within the VCNDD to design and implement experiments to address questions that are central to our lab's interests and funding. The available projects focus on the role of the mGlu7 receptor in the neurodevelopmental disorder Rett syndrome. Successful candidates will receive training in electrophysiology, behavioral neuroscience, molecular pharmacology as well as manuscript and grant writing, all in the context of a team science-oriented academic drug discovery environment. With time, successful candidates will be encouraged to develop their own hypotheses as well as to solicit their own external funding.

Special consideration will be given to candidates with excellent written and oral communication skills, as well as those who are self-motivated, with ability to work independently.

Specific Position Duties with Percentages of Time

[ 90 ]%

Techniques used in this position include, but are not limited to:

Mouse breeding and genetic manipulation

Post-mortem rodent surgery

Biochemical analysis of rodent brains

Preparation of brain slices from rodents

Electrophysiological recordings from brain slices

Neurobehavioral phenotyping in rodents

Cell culture

Molecular cloning

In vitro and in vivo assessment of compound efficacy

Data analysis (knowledge of Microsoft Office, Excel, and Graphpad Prism are a prerequisite)

Presentation of data at meetings both internal and external to the VCNDD

Detailed maintenance of all required notebooks and compound log sheets

[ 10 ]%

Supervision of research assistants, graduate students and undergraduate researchers

Assure trainees adhering to standard lab practice

Mentor career development of junior trainees

Qualifications

Minimum Requirements

Graduation from an accredited college or university with a PhD in neuroscience, pharmacology or a related field

Minimum of 2 first author publications

Ability to work independently, but function as part of a team

Excellent written and oral communication skills

Highly motivated to learn new techniques, develop hypotheses and obtain autonomous funding

Desired or preferred:

Experience with any of the following:

Standard molecular biology techniques

Knowledge of mouse genetics

Brain slice electrophysiology

Knowledge of neurobehavioral assays

Experience formulating compounds is required

Salary and Benefits:

Salary is commensurate with skills and experience.

Application Materials Required: Cover letter Resume/CV Research statement (not to exceed 2 pages) Contact information of 3 professional references Please be advised that Vanderbilt University does check references as part of the employment process.