P Jeffrey Conn

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. ncbi request reprint Metabotropic glutamate receptors in the basal ganglia motor circuit
    P Jeffrey Conn
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 417 D Preson Research Building, Nashville, Tennessee 37232 6600, USA
    Nat Rev Neurosci 6:787-98. 2005
  2. pmc Novel allosteric agonists of M1 muscarinic acetylcholine receptors induce brain region-specific responses that correspond with behavioral effects in animal models
    Gregory J Digby
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Neurosci 32:8532-44. 2012
  3. pmc The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease
    Carrie K Jones
    Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University, Nashville, TN 37212, USA
    J Pharmacol Exp Ther 340:404-21. 2012
  4. pmc mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning
    Jennifer E Ayala
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    Neuropsychopharmacology 34:2057-71. 2009
  5. pmc Further exploration of M₁ allosteric agonists: subtle structural changes abolish M₁ allosteric agonism and result in pan-mAChR orthosteric antagonism
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:223-7. 2013
  6. pmc A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Mol Pharmacol 76:356-68. 2009
  7. pmc Chemical modification of the M(1) agonist VU0364572 reveals molecular switches in pharmacology and a bitopic binding mode
    Gregory J Digby
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    ACS Chem Neurosci 3:1025-36. 2012
  8. pmc 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
    Uyen Le
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:346-50. 2013
  9. ncbi request reprint An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission
    Jana K Shirey
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, 23rd Avenue South at Pierce, Nashville, Tennessee 37232 6600, USA
    Nat Chem Biol 4:42-50. 2008
  10. pmc Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides, sulfonamides and ureas--the effect of capping the distal basic piperidine nitrogen
    Nicole R Miller
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:5443-7. 2008

Detail Information

Publications137 found, 100 shown here

  1. ncbi request reprint Metabotropic glutamate receptors in the basal ganglia motor circuit
    P Jeffrey Conn
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 417 D Preson Research Building, Nashville, Tennessee 37232 6600, USA
    Nat Rev Neurosci 6:787-98. 2005
    ....
  2. pmc Novel allosteric agonists of M1 muscarinic acetylcholine receptors induce brain region-specific responses that correspond with behavioral effects in animal models
    Gregory J Digby
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Neurosci 32:8532-44. 2012
    ....
  3. pmc The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease
    Carrie K Jones
    Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University, Nashville, TN 37212, USA
    J Pharmacol Exp Ther 340:404-21. 2012
    ..The present findings provide exciting support for the potential role of selective mGlu₄ PAMs as a novel approach for the symptomatic treatment of PD and a possible augmentation strategy with either L-DOPA or A2A antagonists...
  4. pmc mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning
    Jennifer E Ayala
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    Neuropsychopharmacology 34:2057-71. 2009
    ..Discovery of small molecules that enhance both LTP and LTD in an activity-appropriate manner shows a unique action on synaptic plasticity that may provide a novel approach for the treatment of impaired cognitive function...
  5. pmc Further exploration of M₁ allosteric agonists: subtle structural changes abolish M₁ allosteric agonism and result in pan-mAChR orthosteric antagonism
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:223-7. 2013
    ....
  6. pmc A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Mol Pharmacol 76:356-68. 2009
    ....
  7. pmc Chemical modification of the M(1) agonist VU0364572 reveals molecular switches in pharmacology and a bitopic binding mode
    Gregory J Digby
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    ACS Chem Neurosci 3:1025-36. 2012
    ..Together, these results suggest that VU0364572 and VU0357017 act as bitopic ligands and that novel antagonists in this series act as competitive orthosteric site antagonists...
  8. pmc 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
    Uyen Le
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:346-50. 2013
    ..In addition, ML253 is selective against the four other muscarinic subtypes, displays excellent CNS exposure and is active in an amphetamine-induced hyperlocomotion assay...
  9. ncbi request reprint An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission
    Jana K Shirey
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, 23rd Avenue South at Pierce, Nashville, Tennessee 37232 6600, USA
    Nat Chem Biol 4:42-50. 2008
    ..Selective regulation of excitatory transmission by M4 suggests that targeting of individual mAChR subtypes could be used to differentially regulate specific aspects of mAChR modulation of function in this important forebrain structure...
  10. pmc Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides, sulfonamides and ureas--the effect of capping the distal basic piperidine nitrogen
    Nicole R Miller
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:5443-7. 2008
    ..Despite the large change in basicity and topology, M1 selectivity was maintained...
  11. pmc Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, 802 Robinson Research Building, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:5439-42. 2008
    ..With slight structural changes, mAChR selectivity was maintained, but the degree of partial M1 agonism varied considerably...
  12. pmc Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats
    Carrie K Jones
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6600, USA
    J Neurosci 28:10422-33. 2008
    ..Together, these data suggest that selective activation of M(1) may provide a novel approach for the treatment of symptoms associated with schizophrenia and Alzheimer's disease...
  13. pmc A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning
    Jana K Shirey
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6600, USA
    J Neurosci 29:14271-86. 2009
    ....
  14. pmc 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
    Mark Turlington
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Center for Structural Biology, and Vanderbilt Institute for Chemical Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    J Med Chem 56:7976-96. 2013
    ..PAM 38t (ML254) will be useful to probe the relative contribution of cooperativity and allosteric agonism to the adverse effect liability and neurotoxicity associated with this class of mGlu5 PAMs. ..
  15. pmc 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
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6600, USA
    Drug Metab Dispos 41:1703-14. 2013
    ..These findings indicate that biotransformation of mGlu5 PAMs to active metabolite-ligands may contribute to the epileptogenesis observed after in vivo administration of this class of allosteric receptor modulators...
  16. pmc M5 receptor activation produces opposing physiological outcomes in dopamine neurons depending on the receptor's location
    Daniel J Foster
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, Departments of Neurology, Psychiatry, and Pharmacology, Columbia University, New York, New York, 10032, Vanderbilt Specialized Chemistry Center for Probe Development, Nashville, Tennessee 37232, and Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232
    J Neurosci 34:3253-62. 2014
    ..Although activation of somatodendritic M5 receptors on SNc neurons leads to increased neuronal firing, activation of M5 receptors in the striatum induces an inhibition in dopamine release...
  17. ncbi request reprint Substituent effects of N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides on positive allosteric modulation of the metabotropic glutamate-5 receptor in rat cortical astrocytes
    Tomas de Paulis
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Med Chem 49:3332-44. 2006
    ..6 +/- 1.9 nM in the binding and functional assays, respectively...
  18. ncbi request reprint Interaction of novel positive allosteric modulators of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor responses
    Yelin Chen
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    Mol Pharmacol 71:1389-98. 2007
    ....
  19. pmc Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity
    Jerri M Rook
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Biol Psychiatry 73:501-9. 2013
    ..This mechanism may be critical to maintaining normal activity-dependence of mGlu5 activation and achieving optimal in vivo effects...
  20. pmc Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Mol Pharmacol 82:860-75. 2012
    ..This model can be applied to PAM and NAM potency curves in combination with maximal fold-shift data to derive reliable estimates of modulator affinities...
  21. ncbi request reprint A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors
    Kamondanai Hemstapat
    Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Pharmacol Exp Ther 322:254-64. 2007
    ..Our data suggest that these two positive allosteric modulators of mGluR2 may share a common binding site and that this site may be distinct from the binding site for the new negative allosteric modulators of group II mGluRs...
  22. pmc Chemical lead optimization of a pan G(q) mAChR M(1), M(3), M(5) positive allosteric modulator (PAM) lead. Part I: Development of the first highly selective M(5) PAM
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:558-62. 2010
    ..An iterative library synthesis approach delivered the first selective M(5) PAM (no activity at M(1)-M(4) @ 30microM), and an important tool compound to study the role of M(5) in the CNS...
  23. pmc Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel mGluR4 positive allosteric modulators
    Colleen M Niswender
    Department of Pharmacology, Vanderbilt University Medical Center, 802 Robinson Research Building, Nashville, TN 37232 6600, USA
    Bioorg Med Chem Lett 18:5626-30. 2008
    ..Despite tremendous therapeutic potential, Compound 7, VU0080421, and related congeners represent only a handful of mGluR4 positive allosteric modulators ever described...
  24. pmc Group III mGluR regulation of synaptic transmission at the SC-CA1 synapse is developmentally regulated
    Jennifer E Ayala
    Department of Pharmacology, Program in Translational Neuropharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Neuropharmacology 54:804-14. 2008
    ....
  25. pmc Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1
    Jason T Manka
    Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:5091-6. 2013
    ....
  26. pmc 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
    Anna L Blobaum
    Drug Metabolism and Pharmacokinetics Laboratory A L B, T M B, F W B, R D M, J S D, Medicinal Chemistry Laboratory M L T, M E M, C W L, S R S, and Molecular Pharmacology Laboratory C K J, C M N, P J C, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee CREATe ADME Tox, C M, and Neuroscience H L, G J M, T S, Janssen Research and Development, Beerse, Belgium and Jarama 75, Toledo, Spain J M B
    Drug Metab Dispos 41:2066-75. 2013
    ....
  27. pmc Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety
    Andrew S Felts
    Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:5779-85. 2013
    ..VU0409106 also proved efficacious in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlu5 antagonists as well as clinically efficacious anxiolytics. ..
  28. pmc N-Acyl-N'-arylpiperazines as negative allosteric modulators of mGlu1: identification of VU0469650, a potent and selective tool compound with CNS exposure in rats
    Kimberly M Lovell
    Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:3713-8. 2013
    ..VU0469650 demonstrated an excellent selectivity profile and good exposure in both plasma and brain samples following intraperitoneal dosing in rats...
  29. ncbi request reprint N-{4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide (CPPHA) acts through a novel site as a positive allosteric modulator of group 1 metabotropic glutamate receptors
    Yelin Chen
    Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 417 D Preston Research Building, Nashville, TN 37232 6600, USA
    Mol Pharmacol 73:909-18. 2008
    ..Together, these data suggest that CPPHA acts at a novel allosteric site on both mGluR1 and -5 to potentiate responses to activation of these receptors...
  30. pmc Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats
    Ashley E Brady
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    J Pharmacol Exp Ther 327:941-53. 2008
    ....
  31. pmc Spirocyclic replacements for the isatin in the highly selective, muscarinic M1 PAM ML137: the continued optimization of an MLPCN probe molecule
    Michael S Poslusney
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:1860-4. 2013
    ..These novel spirocycles possess improved efficacy relative to ML137, while also maintaining high selectivity for the human and rat muscarinic M1 receptor subtype...
  32. pmc Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover
    Jason T Manka
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:6481-5. 2012
    ..These studies suggest that potent PAMs within topologically similar chemotypes can be developed to preferentially interact or not interact with the MPEP allosteric binding site...
  33. pmc 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 (
    Carrie K Jones
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Med Chem 54:7639-47. 2011
    ..Finally, ML182 was shown to be orally active in the haloperidol induced catalepsy model, a well-established antiparkinsonian model...
  34. pmc Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity
    Alice L Rodriguez
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, 2215 Garland Avenue, Nashville, TN 37232 0697, USA
    Mol Pharmacol 78:1105-23. 2010
    ..In addition, these studies provide strong support for the hypothesis that multiple structurally distinct mGluR5 modulators have robust activity in animal models that predict efficacy in the treatment of CNS disorders...
  35. pmc Context-dependent pharmacology exhibited by negative allosteric modulators of metabotropic glutamate receptor 7
    Colleen M Niswender
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Mol Pharmacol 77:459-68. 2010
    ..The pharmacology of this compound represents a striking example of the potential for context-dependent blockade of receptor responses by negative allosteric modulators...
  36. pmc Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4
    Colleen M Niswender
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Mol Pharmacol 74:1345-58. 2008
    ..These exciting results provide continued support for mGluR4 as a therapeutic target in PD...
  37. pmc Allosteric potentiators of metabotropic glutamate receptor subtype 1a differentially modulate independent signaling pathways in baby hamster kidney cells
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States
    Neuropharmacology 55:419-27. 2008
    ..Together, these data provide further evidence that allosteric compounds can differentially modulate the coupling of a single receptor to independent signaling pathways or act in a system-dependent manner...
  38. pmc 3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats
    Andrew S Felts
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:4390-4. 2010
    ..Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples...
  39. pmc Probing the metabotropic glutamate receptor 5 (mGlu₅) positive allosteric modulator (PAM) binding pocket: discovery of point mutations that engender a "molecular switch" in PAM pharmacology
    Karen J Gregory
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Mol Pharmacol 83:991-1006. 2013
    ..Interestingly, we identified two point mutations in TMs 6 and 7 that, when mutated, engender a mode switch in the pharmacology of certain PAMs...
  40. pmc Isatin replacements applied to the highly selective, muscarinic M1 PAM ML137: continued optimization of an MLPCN probe molecule
    Bruce J Melancon
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 23:412-6. 2013
    ..Muscarinic receptor subtype selectivity for the M(1) receptor was also maintained...
  41. pmc The metabotropic glutamate receptor 8 agonist (S)-3,4-DCPG reverses motor deficits in prolonged but not acute models of Parkinson's disease
    Kari A Johnson
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA
    Neuropharmacology 66:187-95. 2013
    ..This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'...
  42. pmc 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
    James C Tarr
    Department of Pharmacology, Department of Chemistry, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt Specialized Chemistry Center for Probe Development MLPCN, and Vanderbilt Institute of Chemical Biology Chemical Synthesis Core, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    ACS Chem Neurosci 3:884-95. 2012
    ..Selected analogues were able to potentiate CCh-mediated nonamyloidogenic APPsα release, further strengthening the concept that M(1) PAMs may afford a disease-modifying role in the treatment of AD...
  43. pmc Development of novel M1 antagonist scaffolds through the continued optimization of the MLPCN probe ML012
    Bruce J Melancon
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:5035-40. 2012
    ..Data for representative molecules 7w (VU0452865) and 12a (VU0455691) are presented...
  44. pmc Functional impact of allosteric agonist activity of selective positive allosteric modulators of metabotropic glutamate receptor subtype 5 in regulating central nervous system function
    Meredith J Noetzel
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232 0697, USA
    Mol Pharmacol 81:120-33. 2012
    ..These data suggest that the level of receptor expression influences the ability of mGlu(5) PAMs to act as allosteric agonists in vitro and that ago-PAM activity observed in cell-based assays may not be important for in vivo efficacy...
  45. pmc Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)
    Darren W Engers
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:5175-8. 2010
    ..An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu(4) PAM reported to date...
  46. pmc Metabotropic glutamate receptors mGluR4 and mGluR8 regulate transmission in the lateral olfactory tract-piriform cortex synapse
    Paulianda J Jones
    Department of Pharmacology, Program in Translational Neuropharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Neuropharmacology 55:440-6. 2008
    ..The high potency of L-AP4, combined with the observed effects of DCPG and PHCCC, suggests that both mGluR4 and mGluR8 play a role in the l-AP4-induced inhibition of synaptic transmission at the LOT-PC synapse...
  47. pmc Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity
    Joy E Marlo
    Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Mol Pharmacol 75:577-88. 2009
    ..These data also suggest that structurally diverse M(1) potentiators may act by distinct mechanisms and differentially regulate receptor coupling to downstream signaling pathways...
  48. pmc 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
    Russell J Amato
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    ACS Chem Neurosci 4:1217-28. 2013
    ..The utility of 29 (VU0463841) was demonstrated by its ability to attenuate drug seeking behaviors in relevant rat models of cocaine addiction. ..
  49. pmc Discovery and SAR of a novel series of non-MPEP site mGlu₅ PAMs based on an aryl glycine sulfonamide scaffold
    Alice L Rodriguez
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:7388-92. 2012
    ..This series represents a rare non-MPEP site mGlu(5) PAM chemotype...
  50. pmc Discovery of (R)-(2-fluoro-4-((-4-methoxyphenyl)ethynyl)phenyl) (3-hydroxypiperidin-1-yl)methanone (ML337), an mGlu3 selective and CNS penetrant negative allosteric modulator (NAM)
    Cody J Wenthur
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Med Chem 56:5208-12. 2013
    ..92 (mouse) to 0.3 (rat). DMPK profiling and shallow SAR led to the incorporation of deuterium atoms to address a metabolic soft spot, which subsequently lowered both in vitro and in vivo clearance by >50%. ..
  51. pmc Impact of isoflurane anesthesia on D2 receptor occupancy by [18F]fallypride measured by microPET with a modified Logan plot
    Mohammed N Tantawy
    Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Synapse 65:1173-80. 2011
    ..In this work, we use this method to assess the effects of isoflurane anesthesia on [(18) F]fallypride DVR'...
  52. pmc 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
    James M Salovich
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:5084-8. 2012
    ..ML293 was also selective versus the other muscarinic subtypes and displayed excellent in vivo PK properties in rat with low IV clearance (11.6 mL/min/kg) and excellent brain exposure (PO PBL, 10 mg/kg at 1h, [Brain]=10.3 μM, B:P=0.85)...
  53. pmc Activation of group II metabotropic glutamate receptors induces long-term depression of excitatory synaptic transmission in the substantia nigra pars reticulata
    Kari A Johnson
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA
    Neurosci Lett 504:102-6. 2011
    ..These studies suggest a novel role for mGlu2 in the long-term regulation of excitatory transmission in the SNr and invite further exploration of mGlu2 as a therapeutic target for treating the motor symptoms of PD...
  54. pmc Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4)
    Richard Williams
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:4967-70. 2009
    ..The synthesis takes advantage of an iterative parallel synthesis approach to rapidly synthesize and evaluate a number of analogs of VU0155041...
  55. pmc Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS
    Ya Zhou
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:6502-6. 2009
    ..This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and further examples of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold...
  56. ncbi request reprint Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in mice
    Ruggero Galici
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Ave S at Pierce, 417 D Preston Research Building, Nashville, TN 37232 6600, USA
    J Pharmacol Exp Ther 318:173-85. 2006
    ....
  57. pmc 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
    Jeffrey P Lamb
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 21:2711-4. 2011
    ..An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu(5) NAMs, mGlu(5) PAMs as well as mGlu(5) partial antagonists...
  58. ncbi request reprint The antipsychotic potential of muscarinic allosteric modulation
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Drug News Perspect 23:229-40. 2010
    ..These data suggest that selective allosteric activation of either M(1) or M(4) has antipsychotic potential through distinct, yet complimentary mechanisms...
  59. pmc Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS
    Shen Yin
    Department of Pharmacology and the Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee 37232, and Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia
    J Neurosci 34:79-94. 2014
    ..These data greatly extend our current understanding of mGlu receptor interaction and function and provide compelling evidence that mGlu receptors can function as heteromers in intact brain circuits. ..
  60. pmc Continued optimization of the MLPCN probe ML071 into highly potent agonists of the hM1 muscarinic acetylcholine receptor
    Bruce J Melancon
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:3467-72. 2012
    ..These results and the implications of a bitopic mode of action are presented...
  61. pmc Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012
    Bruce J Melancon
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:1044-8. 2012
    ..Muscarinic subtype selectivity across all five human and rat receptors for 13l, along with rat selectivity for the lead compound (ML012), is presented...
  62. pmc Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins
    Thomas M Bridges
    Vanderbilt Program in Drug Discovery, Department of Pharmacology and Chemistry, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    J Med Chem 52:3445-8. 2009
    ..Subsequent optimization led to the discovery of VU0238429, which possessed an EC(50) of approximately 1.16 microM at M5 with >30-fold selectivity versus M1 and M3, with no M2 or M4 potentiator activity...
  63. pmc Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, Nashville, TN 37232, USA
    Trends Pharmacol Sci 30:148-55. 2009
    ....
  64. pmc 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
    Darren W Engers
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    J Med Chem 54:1106-10. 2011
    ..Compounds from the series show submicromolar potency at both human and rat mGlu(4). In addition, pharmacokinetic studies utilizing subcutaneous dosing demonstrated good brain exposure in rats...
  65. pmc Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold
    Richard Williams
    Department of Pharmacology, Vanderbilt Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 21:1350-3. 2011
    ....
  66. pmc Discovery of molecular switches that modulate modes of metabotropic glutamate receptor subtype 5 (mGlu5) pharmacology in vitro and in vivo within a series of functionalized, regioisomeric 2- and 5-(phenylethynyl)pyrimidines
    Sameer Sharma
    Department of Chemistry, Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Med Chem 52:4103-6. 2009
    ....
  67. pmc Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273
    Darren W Engers
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    ChemMedChem 4:505-11. 2009
    ..The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties...
  68. doi request reprint A novel assay of Gi/o-linked G protein-coupled receptor coupling to potassium channels provides new insights into the pharmacology of the group III metabotropic glutamate receptors
    Colleen M Niswender
    1215 MRB IV, Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Mol Pharmacol 73:1213-24. 2008
    ..We anticipate that the GIRK-mediated thallium flux strategy will provide a novel tool to advance the study of G(i/o)-coupled GPCR biology and promote ligand discovery and characterization...
  69. pmc Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead
    Richard Williams
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:962-6. 2009
    ..However, this work highlights the challenges in hit-to-lead for mGluR4 PAMs, with multiple confirmed HTS hits displaying little or no tractable SAR...
  70. pmc Synthesis and SAR of a mGluR5 allosteric partial antagonist lead: unexpected modulation of pharmacology with slight structural modifications to a 5-(phenylethynyl)pyrimidine scaffold
    Sameer Sharma
    Department of Pharmacology, Vanderbilt University Medical Center, 12415D MRBIV, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:4098-101. 2008
    ....
  71. pmc Synthesis and SAR of N-(4-(4-alklylpiperazin-1-yl)phenyl)benzamides as muscarinic acetylcholine receptor subtype 1 (M1) anatgonists
    Nicole R Miller
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:2174-7. 2010
    ..Compounds in this series possess M(1) antagonist IC(50)s in the 350 nM to >10 microM range with varying degrees of functional selectivity versus M(2)-M(5)...
  72. pmc Functional selectivity induced by mGlu₄ receptor positive allosteric modulation and concomitant activation of Gq coupled receptors
    Shen Yin
    Vanderbilt Center for Neuroscience Drug Discovery, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Neuropharmacology 66:122-32. 2013
    ..This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'...
  73. pmc Roles of the M1 muscarinic acetylcholine receptor subtype in the regulation of basal ganglia function and implications for the treatment of Parkinson's disease
    Zixiu Xiang
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    J Pharmacol Exp Ther 340:595-603. 2012
    ....
  74. pmc Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): the development of ML169, an MLPCN probe
    Paul R Reid
    Vanderbilt Institute of Chemical Biology Chemical Synthesis Core, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 21:2697-701. 2011
    ....
  75. pmc Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5
    Andrew S Felts
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:6623-6. 2009
    ..This Letter describes the SAR of this series and the profile of selected compounds in selectivity and radioligand binding assays...
  76. pmc Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu5 PAM
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 22:3921-5. 2012
    ..This NAM (VU0463597, ML289) displays an IC(50) value of 0.66 μM and is inactive against mGlu(5)...
  77. pmc Targeting glutamate synapses in schizophrenia
    Julie R Field
    Department of Pharmacology and Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37212, USA
    Trends Mol Med 17:689-98. 2011
    ....
  78. ncbi request reprint A novel class of positive allosteric modulators of metabotropic glutamate receptor subtype 1 interact with a site distinct from that of negative allosteric modulators
    Kamondanai Hemstapat
    Department of Pharmacology, Vanderbilt University Medical Center, 23rd Ave South at Pierce, 417 D Preston Research Bldg, Nashville, TN 37232 6600, USA
    Mol Pharmacol 70:616-26. 2006
    ..Site-directed mutagenesis revealed that valine at position 757 in transmembrane V of mGluR1a is crucial for the activity of multiple classes of allosteric mGluR1 potentiators...
  79. pmc Heterobiaryl and heterobiaryl ether derived M5 positive allosteric modulators
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:5617-22. 2010
    ..An iterative parallel synthesis approach was employed to incorporate basic heterocycles to improve physiochemical properties...
  80. pmc Discovery and SAR of novel mGluR5 non-competitive antagonists not based on an MPEP chemotype
    Alice L Rodriguez
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 19:3209-13. 2009
    ..This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and the first example of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold...
  81. pmc Solution-phase parallel synthesis and SAR of homopiperazinyl analogs as positive allosteric modulators of mGlu₄
    Yiu Yin Cheung
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, United States
    ACS Comb Sci 13:159-65. 2011
    ..This series of positive allosteric modulators of mGlu₄ provide critical research tools to further probe the mGlu₄-mediated effects in Parkinson's disease...
  82. pmc Chemical lead optimization of a pan Gq mAChR M1, M3, M5 positive allosteric modulator (PAM) lead. Part II: development of a potent and highly selective M1 PAM
    Thomas M Bridges
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 20:1972-5. 2010
    ..An iterative library synthesis approach delivered a potent (M(1) EC(50)=830 nM) and highly selective M(1) PAM (>30 microM vs M(2)-M(5))...
  83. pmc "Molecular switches" on mGluR allosteric ligands that modulate modes of pharmacology
    Michael R Wood
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States
    Biochemistry 50:2403-10. 2011
    ..Here, we will discuss the impact of modest structural changes to multiple mGluR allosteric ligands scaffolds that unexpectedly modulate pharmacology and raise concerns over metabolism and the pharmacology of metabolites...
  84. pmc Orthosteric- and allosteric-induced ligand-directed trafficking at GPCRs
    Gregory J Digby
    Vanderbilt University School of Medicine, Department of Pharmacology, 12415D MRBIV Langford, Nashville, TN 37232, USA
    Curr Opin Drug Discov Devel 13:587-94. 2010
    ..This review discusses recent studies in which both orthosteric and allosteric compounds have been demonstrated to induce LDTRS...
  85. ncbi request reprint A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtype 5 and blocks the effects of multiple allosteric modulators
    Alice L Rodriguez
    Department of Pharmacology and Program in Translational Neuropharmacology, Vanderbilt University Medical Center, 23rd Ave South at Pierce, 417 D Preston Research Bldg, Nashville, Tennessee 37232 6600, USA
    Mol Pharmacol 68:1793-802. 2005
    ..These novel compounds provide valuable new insight into the pharmacology of allosteric sites on G protein-coupled receptors and provide valuable new tools for determining the effects of allosteric site ligands in native systems...
  86. pmc Allosteric modulation of metabotropic glutamate receptors
    Douglas J Sheffler
    Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Adv Pharmacol 62:37-77. 2011
    ..Studies continue to validate the therapeutic utility of mGlu allosteric modulators as a potential therapeutic approach for a number of disorders including anxiety, schizophrenia, Parkinson's disease, and Fragile X syndrome...
  87. pmc Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)
    Darren W Engers
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    J Med Chem 52:4115-8. 2009
    ..Compounds 9b and 9c showed submicromolar potency at both human and rat mGluR4. In addition, both 9b and 9c were shown to be centrally penetrant in rats using nontoxic vehicles, a major advance for the mGluR4 field...
  88. pmc Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, 1215 Light Hall, Nashville, Tennessee 37232, USA
    Nat Rev Drug Discov 8:41-54. 2009
    ..These compounds provide high selectivity, novel modes of efficacy and may lead to novel therapeutic agents for the treatment of multiple psychiatric and neurological human disorders...
  89. ncbi request reprint Allosteric potentiators of metabotropic glutamate receptor subtype 5 have differential effects on different signaling pathways in cortical astrocytes
    Yongqin Zhang
    Program in Translational Neuropharmacology, Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Pharmacol Exp Ther 315:1212-9. 2005
    ..Together, these data provide evidence that different allosteric potentiators can differentially modulate coupling of a single receptor to different signaling pathways...
  90. pmc Glutamate receptors as therapeutic targets for Parkinson's disease
    Kari A Johnson
    Department of Pharmacology, Vanderbilt University, Nashville, TN, USA
    CNS Neurol Disord Drug Targets 8:475-91. 2009
    ..These drugs reverse motor deficits in addition to providing protection against neurodegeneration. Glutamate receptors therefore represent exciting targets for the development of novel pharmacological therapies for PD...
  91. ncbi request reprint A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2/3 receptor agonist in mouse models predictive of antipsychotic activity
    Ruggero Galici
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 417 D Preston Research Building, Nashville, TN 37232 6600, USA
    J Pharmacol Exp Ther 315:1181-7. 2005
    ..Furthermore, these data raise the possibility that a selective allosteric potentiator of mGlu2 receptor could have utility as a novel approach for the treatment of schizophrenia...
  92. pmc Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Medical Center, Nashville, TN, USA
    Trends Pharmacol Sci 30:25-31. 2009
    ..These mGlu receptor-selective PAMs have properties needed for optimization as clinical candidates and have robust effects in animal models that predict efficacy in treatment of schizophrenia...
  93. ncbi request reprint New therapeutic frontiers for metabotropic glutamate receptors
    Colleen M Niswender
    Program in Translational Neuropharmacology, Department of Pharmacology, Vanderbilt University Medical Center, 23rd Avenue South at Pierce, 452 B Preston Research Building, Nashville, TN 37232 6600, USA
    Curr Top Med Chem 5:847-57. 2005
    ..These studies suggest the exciting possibility that drugs active at mGlu receptors will be useful in treatment of a wide variety of neurological and psychiatric disorders such as Parkinson's disease, anxiety disorders, and schizophrenia...
  94. ncbi request reprint A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis
    Michael A Benneyworth
    Department of Pharmacology, Vanderbilt University School of Medicine, 8140 MRB III, Nashville, TN 37232, USA
    Mol Pharmacol 72:477-84. 2007
    ....
  95. pmc Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists
    L Michelle Lewis
    Vanderbilt Program in Drug Discovery, Vanderbilt Institute of Chemical Biology, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 18:885-90. 2008
    ..Compounds in this series possess M1 antagonist IC(50)s in the 441nM-19microM range with 8- to >340-fold functional selectivity versus rM2-rM5...
  96. pmc Allosteric modulation of metabotropic glutamate receptors: structural insights and therapeutic potential
    Karen J Gregory
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 0697, USA
    Neuropharmacology 60:66-81. 2011
    ..In the absence of a class C GPCR crystal structure, this approach has shown promise with respect to the interpretation of mutagenesis data and understanding structure-activity relationships of allosteric modulator pharmacophores...
  97. doi request reprint Schizophrenia: moving beyond monoamine antagonists
    P Jeffrey Conn
    Vanderbilt University, Department of Pharmacology, Nashville, TN 37232, USA
    Mol Interv 8:99-107. 2008
    ..Current attempts to target a new range of receptors entail unprecedented fine-tuning in the pharmacological manipulation of specific receptor subtypes...
  98. pmc [(18)F]Fallypride dopamine D2 receptor studies using delayed microPET scans and a modified Logan plot
    Mohammed N Tantawy
    Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Nashville, TN 37232, USA
    Nucl Med Biol 36:931-40. 2009
    ..In particular, we applied a modified version of the Logan plot method on the last 60 min of 120-min data and compared the results to those from analysis of the full data set...
  99. doi request reprint Allosteric activators of muscarinic receptors as novel approaches for treatment of CNS disorders
    Gregory J Digby
    Mol Biosyst 6:1345-54. 2010
    ..These novel allosteric modulators of mAChRs may provide therapeutic potential for treatment of a number of CNS disorders such as Alzheimer's disease and schizophrenia...
  100. pmc Metabotropic glutamate receptors: physiology, pharmacology, and disease
    Colleen M Niswender
    Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37212, USA
    Annu Rev Pharmacol Toxicol 50:295-322. 2010
    ....
  101. doi request reprint Opportunities and challenges of psychiatric drug discovery: roles for scientists in academic, industry, and government settings
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
    Neuropsychopharmacology 33:2048-60. 2008
    ..Also, increased attention should be focused on the development of early predictors of adverse effects of candidate compounds...