Published in Mol Pharmacol on December 04, 2007
Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat Rev Drug Discov (2009) 6.69
Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia. Trends Pharmacol Sci (2008) 3.22
Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders. Trends Pharmacol Sci (2009) 2.38
Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4. Mol Pharmacol (2008) 1.94
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 (2010) 1.93
Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science (2014) 1.81
mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology (2009) 1.80
Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol Pharmacol (2008) 1.68
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 (2011) 1.46
Allosteric modulation of metabotropic glutamate receptors: structural insights and therapeutic potential. Neuropharmacology (2010) 1.30
Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology. ACS Chem Neurosci (2010) 1.24
Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol Psychiatry (2012) 1.22
Identification of Metabotropic Glutamate Receptor Subtype 5 Potentiators Using Virtual High-Throughput Screening. ACS Chem Neurosci (2010) 1.16
Investigating metabotropic glutamate receptor 5 allosteric modulator cooperativity, affinity, and agonism: enriching structure-function studies and structure-activity relationships. Mol Pharmacol (2012) 1.15
Metabotropic glutamate receptors as therapeutic targets for schizophrenia. Neuropharmacology (2011) 1.10
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. Mol Pharmacol (2013) 1.05
Discovery of N-Aryl Piperazines as Selective mGlu(5) Potentiators with Efficacy in a Rodent Model Predictive of Anti-Psychotic Activity. ACS Med Chem Lett (2010) 1.04
A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling. Mol Pharmacol (2013) 1.04
Novel Allosteric Modulators of G Protein-coupled Receptors. J Biol Chem (2015) 1.02
Positive allosteric modulators of type 5 metabotropic glutamate receptors (mGluR5) and their therapeutic potential for the treatment of CNS disorders. Molecules (2011) 0.99
Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS. Bioorg Med Chem Lett (2009) 0.99
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 (2013) 0.96
Relationship between in vivo receptor occupancy and efficacy of metabotropic glutamate receptor subtype 5 allosteric modulators with different in vitro binding profiles. Neuropsychopharmacology (2014) 0.94
Optimization of an ether series of mGlu5 positive allosteric modulators: molecular determinants of MPEP-site interaction crossover. Bioorg Med Chem Lett (2012) 0.94
Allosteric modulation of metabotropic glutamate receptors. Adv Pharmacol (2011) 0.91
Metabotropic glutamate receptor subtype 5: molecular pharmacology, allosteric modulation and stimulus bias. Br J Pharmacol (2015) 0.88
Structure and ligand recognition of class C GPCRs. Acta Pharmacol Sin (2012) 0.86
Quantitative analysis reveals multiple mechanisms of allosteric modulation of the mGlu5 receptor in rat astroglia. Mol Pharmacol (2011) 0.85
Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5. Bioorg Med Chem Lett (2010) 0.84
Effects of positive allosteric modulators on single-cell oscillatory Ca2+ signaling initiated by the type 5 metabotropic glutamate receptor. Mol Pharmacol (2009) 0.83
Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation. Mol Pharmacol (2015) 0.83
Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indications. Cell Signal (2014) 0.81
Glutamatergic regulation of cognition and functional brain connectivity: insights from pharmacological, genetic and translational schizophrenia research. Br J Pharmacol (2017) 0.79
Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor. Cell Res (2016) 0.78
Organization and functions of mGlu and GABAB receptor complexes. Nature (2016) 0.77
VU0477573: Partial Negative Allosteric Modulator of the Subtype 5 Metabotropic Glutamate Receptor with In Vivo Efficacy. J Pharmacol Exp Ther (2015) 0.77
Structural insight to mutation effects uncover a common allosteric site in class C GPCRs. Bioinformatics (2016) 0.75
Modulation of neuronal microcircuit activities within the medial prefrontal cortex by mGluR5 positive allosteric modulator. J Psychopharmacol (2014) 0.75
Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol (2010) 4.77
IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic Acids Res (2008) 3.76
Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies: application to GPCR oligomerization. Nat Methods (2008) 2.88
A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models. J Pharmacol Exp Ther (2004) 2.83
Closed state of both binding domains of homodimeric mGlu receptors is required for full activity. Nat Struct Mol Biol (2004) 2.58
Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo. J Med Chem (2004) 2.46
Building a new conceptual framework for receptor heteromers. Nat Chem Biol (2009) 2.41
Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in rats. J Neurosci (2008) 2.34
Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J Pharmacol Exp Ther (2008) 2.29
A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5. Mol Pharmacol (2003) 2.27
A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain. J Pharmacol Exp Ther (2004) 2.17
Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA. Bioorg Med Chem Lett (2006) 2.17
Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat Chem Biol (2010) 2.15
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 (2008) 2.12
Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery. J Med Chem (2012) 2.10
Virtual screening workflow development guided by the "receiver operating characteristic" curve approach. Application to high-throughput docking on metabotropic glutamate receptor subtype 4. J Med Chem (2005) 2.06
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. Mol Pharmacol (2005) 2.03
Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment. Proc Natl Acad Sci U S A (2003) 1.98
N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity. Proc Natl Acad Sci U S A (2003) 1.96
Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4. Mol Pharmacol (2008) 1.94
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 (2010) 1.93
"Molecular switches" on mGluR allosteric ligands that modulate modes of pharmacology. Biochemistry (2011) 1.89
An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission. Nat Chem Biol (2007) 1.83
G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives. Pharmacol Rev (2014) 1.82
Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science (2014) 1.81
mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology (2009) 1.80
Glutamate-based therapeutic approaches: allosteric modulators of metabotropic glutamate receptors. Curr Opin Pharmacol (2005) 1.80
Synthesis and SAR of a mGluR5 allosteric partial antagonist lead: unexpected modulation of pharmacology with slight structural modifications to a 5-(phenylethynyl)pyrimidine scaffold. Bioorg Med Chem Lett (2008) 1.78
A novel selective muscarinic acetylcholine receptor subtype 1 antagonist reduces seizures without impairing hippocampus-dependent learning. Mol Pharmacol (2009) 1.76
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. J Med Chem (2006) 1.73
Evidence for a single heptahelical domain being turned on upon activation of a dimeric GPCR. EMBO J (2005) 1.72
Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity. Mol Pharmacol (2008) 1.68
Asymmetric conformational changes in a GPCR dimer controlled by G-proteins. EMBO J (2006) 1.66
Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in mice. J Pharmacol Exp Ther (2006) 1.60
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) 1.59
Allosteric modulators of group I metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives. Curr Opin Pharmacol (2002) 1.58
Activation of a dimeric metabotropic glutamate receptor by intersubunit rearrangement. J Biol Chem (2007) 1.57
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) 1.57
A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning. J Neurosci (2009) 1.57
Group III metabotropic glutamate receptor-mediated modulation of the striatopallidal synapse. J Neurosci (2003) 1.55
Asymmetric functioning of dimeric metabotropic glutamate receptors disclosed by positive allosteric modulators. J Biol Chem (2005) 1.55
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) 1.52
A single subunit (GB2) is required for G-protein activation by the heterodimeric GABA(B) receptor. J Biol Chem (2001) 1.49
Direct and indirect modulation of the N-methyl D-aspartate receptor. Curr Drug Targets CNS Neurol Disord (2002) 1.49
Dimers and beyond: The functional puzzles of class C GPCRs. Pharmacol Ther (2011) 1.48
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 (2011) 1.46
Interaction of novel positive allosteric modulators of metabotropic glutamate receptor 5 with the negative allosteric antagonist site is required for potentiation of receptor responses. Mol Pharmacol (2007) 1.46
The heptahelical domain of GABA(B2) is activated directly by CGP7930, a positive allosteric modulator of the GABA(B) receptor. J Biol Chem (2004) 1.45
Glutamate receptors and Parkinson's disease: opportunities for intervention. Drugs Aging (2003) 1.44
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. J Pharmacol Exp Ther (2005) 1.43
A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis. Mol Pharmacol (2007) 1.42
Allosteric potentiators of metabotropic glutamate receptor subtype 5 have differential effects on different signaling pathways in cortical astrocytes. J Pharmacol Exp Ther (2005) 1.42
Cell surface detection of membrane protein interaction with homogeneous time-resolved fluorescence resonance energy transfer technology. Anal Biochem (2004) 1.40
The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc Natl Acad Sci U S A (2003) 1.40
CRF receptor 1 regulates anxiety behavior via sensitization of 5-HT2 receptor signaling. Nat Neurosci (2010) 1.38
Metabotropic glutamate subtype 5 receptors modulate locomotor activity and sensorimotor gating in rodents. J Pharmacol Exp Ther (2003) 1.38
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. Bioorg Med Chem Lett (2010) 1.37
No ligand binding in the GB2 subunit of the GABA(B) receptor is required for activation and allosteric interaction between the subunits. J Neurosci (2002) 1.36
International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Pharmacol Rev (2005) 1.35
Crosstalk between GABAB and mGlu1a receptors reveals new insight into GPCR signal integration. EMBO J (2009) 1.32
Allosteric modulation of metabotropic glutamate receptors: structural insights and therapeutic potential. Neuropharmacology (2010) 1.30
Glutamate receptors as therapeutic targets for Parkinson's disease. CNS Neurol Disord Drug Targets (2009) 1.30
PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. Hum Mol Genet (2008) 1.30
Synthesis and structure-activity relationships of allosteric potentiators of the m(4) muscarinic acetylcholine receptor. ChemMedChem (2009) 1.29
Synthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273. ChemMedChem (2009) 1.29
Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks. Curr Top Med Chem (2013) 1.28
A new approach to analyze cell surface protein complexes reveals specific heterodimeric metabotropic glutamate receptors. FASEB J (2010) 1.27
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 (2010) 1.27
A novel class of positive allosteric modulators of metabotropic glutamate receptor subtype 1 interact with a site distinct from that of negative allosteric modulators. Mol Pharmacol (2006) 1.26
Locking the dimeric GABA(B) G-protein-coupled receptor in its active state. J Neurosci (2004) 1.25
A single olfactory receptor specifically binds a set of odorant molecules. Eur J Neurosci (2002) 1.25
Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology. ACS Chem Neurosci (2010) 1.24
Group III metabotropic glutamate-receptor-mediated modulation of excitatory transmission in rodent substantia nigra pars compacta dopamine neurons. J Pharmacol Exp Ther (2005) 1.24
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. Bioorg Med Chem Lett (2009) 1.23
The metabotropic glutamate receptor mGluR5 is endocytosed by a clathrin-independent pathway. J Biol Chem (2003) 1.23
The mGluR2 positive allosteric modulator BINA decreases cocaine self-administration and cue-induced cocaine-seeking and counteracts cocaine-induced enhancement of brain reward function in rats. Neuropsychopharmacology (2010) 1.23
Distinct physiological roles of the Gq-coupled metabotropic glutamate receptors Co-expressed in the same neuronal populations. J Cell Physiol (2002) 1.22
Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity. Biol Psychiatry (2012) 1.22
G protein activation by serotonin type 4 receptor dimers: evidence that turning on two protomers is more efficient. J Biol Chem (2011) 1.21
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 (2010) 1.21
Closure of the Venus flytrap module of mGlu8 receptor and the activation process: Insights from mutations converting antagonists into agonists. Proc Natl Acad Sci U S A (2002) 1.21
The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats. Psychopharmacology (Berl) (2004) 1.21
Development of allosteric modulators of GPCRs for treatment of CNS disorders. Neurobiol Dis (2013) 1.20
Probing the existence of G protein-coupled receptor dimers by positive and negative ligand-dependent cooperative binding. Mol Pharmacol (2006) 1.20
Metabotropic receptors for glutamate and GABA in pain. Brain Res Rev (2008) 1.20
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 (2008) 1.19
Real-time analysis of agonist-induced activation of protease-activated receptor 1/Galphai1 protein complex measured by bioluminescence resonance energy transfer in living cells. Mol Pharmacol (2007) 1.17
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 (2014) 1.17
A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors. J Pharmacol Exp Ther (2007) 1.16
Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead. Bioorg Med Chem Lett (2008) 1.16
Identification of Metabotropic Glutamate Receptor Subtype 5 Potentiators Using Virtual High-Throughput Screening. ACS Chem Neurosci (2010) 1.16
Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties. Bioorg Med Chem Lett (2008) 1.15
The antipsychotic potential of muscarinic allosteric modulation. Drug News Perspect (2010) 1.15