4.7 Review

Fine Tuning Muscarinic Acetylcholine Receptor Signaling Through Allostery and Bias

Related references

Note: Only part of the references are listed.
Article Chemistry, Medicinal

Development of Novel 4-Arylpyridin-2-one and 6-Arylpyrimidin-4-one Positive Allosteric Modulators of the M1Muscarinic Acetylcholine Receptor

Manuela Jorg et al.

Summary: This study investigated the structure-activity relationships of 4-phenylpyridin-2-one and 6-phenylpyrimidin-4-one M(1)muscarinic acetylcholine receptor positive allosteric modulators (PAMs), showing that modifications to the analogues result in nuanced effects on the allosteric properties. The research also found that despite primarily acting as affinity modulators, the PAMs displayed different pharmacological properties across the two cellular assays. The novel PAM7 was identified as a potential lead candidate for further development due to its lower BBB permeability and improved exposure in the periphery compared to lead2.

CHEMMEDCHEM (2021)

Article Chemistry, Medicinal

Discovery of structurally distinct tricyclic M4 positive allosteric modulator (PAM) chemotypes

Kayla J. Temple et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2020)

Article Chemistry, Medicinal

Discovery of a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide M4 positive allosteric modulator (PAM) chemotype

Kayla J. Temple et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2020)

Article Biochemistry & Molecular Biology

Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs

Sophie J. Bradley et al.

NATURE CHEMICAL BIOLOGY (2020)

Article Biochemistry & Molecular Biology

Discovery of Tricyclic Triazolo- and Imidazopyridine Lactams as M1 Positive Allosteric Modulators

Julie L. Engers et al.

ACS CHEMICAL NEUROSCIENCE (2019)

Review Neurosciences

The Role of PI3K/Akt and ERK in Neurodegenerative Disorders

Sachchida Nand Rai et al.

NEUROTOXICITY RESEARCH (2019)

Article Chemistry, Medicinal

VU6005806/AZN-00016130, an advanced M4 positive allosteric modulator (PAM) profiled as a potential preclinical development candidate

Darren W. Engers et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2019)

Article Multidisciplinary Sciences

14-3-3 signal adaptor and scaffold proteins mediate GPCR trafficking

Luwa Yuan et al.

SCIENTIFIC REPORTS (2019)

Article Chemistry, Medicinal

Discovery of a novel 3,4-dimethylcinnoline carboxamide M4 positive allosteric modulator (PAM) chemotype via scaffold hopping

Kayla J. Temple et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2019)

Article Clinical Neurology

Widespread Changes in Positive Allosteric Modulation of the Muscarinic M1 Receptor in Some Participants With Schizophrenia

Shaun Hopper et al.

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY (2019)

Article Biochemistry & Molecular Biology

6-Phenylpyrimidin-4-ones as Positive Allosteric Modulators at the M1 mAChR: The Determinants of Allosteric Activity

Manuela Jorg et al.

ACS CHEMICAL NEUROSCIENCE (2019)

Article Psychiatry

Region-specific inhibition of 14-3-3 proteins induces psychomotor behaviors in mice

Kourtney Graham et al.

NPJ SCHIZOPHRENIA (2019)

Article Multidisciplinary Sciences

Generation of a whole-brain atlas for the cholinergic system and mesoscopic projectome analysis of basal forebrain cholinergic neurons

Xiangning Li et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Article Chemistry, Medicinal

The discovery of VU0486846: steep SAR from a series of M-1 PAMs based on a novel benzomorpholine core

Jeanette L. Bertron et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2018)

Review Biotechnology & Applied Microbiology

Biased signalling: from simple switches to allosteric microprocessors

Jeffrey S. Smith et al.

NATURE REVIEWS DRUG DISCOVERY (2018)

Article Multidisciplinary Sciences

Lifetime of muscarinic receptor-G-protein complexes determines coupling efficiency and G-protein subtype selectivity

Olga S. Ilyaskina et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Article Chemistry, Medicinal

MK-7622: A First-in-Class M1 Positive Allosteric Modulator Development Candidate

Douglas C. Beshore et al.

ACS MEDICINAL CHEMISTRY LETTERS (2018)

Review Cell Biology

Mechanisms of signalling and biased agonism in G protein-coupled receptors

Denise Wootten et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2018)

Article Medicine, Research & Experimental

M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss

Sophie J. Bradley et al.

JOURNAL OF CLINICAL INVESTIGATION (2017)

Article Chemistry, Medicinal

Discovery of VU0467485/AZ13713945: An M4 PAM Evaluated as a Preclinical Candidate for the Treatment of Schizophrenia

Michael R. Wood et al.

ACS MEDICINAL CHEMISTRY LETTERS (2017)

Article Multidisciplinary Sciences

Muscarinic receptor regulates extracellular signal regulated kinase by two modes of arrestin binding

Seung-Ryoung Jung et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

Article Chemistry, Medicinal

Discovery of the first low-shift positive allosteric modulators for the muscarinic M1 receptor

Alexander Flohr et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2017)

Article Chemistry, Medicinal

Discovery of a novel 2,4-dimethylquinoline-6-carboxamide M4 positive allosteric modulator (PAM) chemotype via scaffold hopping

Madeline F. Long et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2017)

Article Chemistry, Medicinal

Discovery of a novel, CNS penetrant M4 PAM chemotype based on a 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core

Blake R. Bewley et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2017)

Article Psychiatry

Abnormalities of signal transduction networks in chronic schizophrenia

Jennifer L. McGuire et al.

NPJ SCHIZOPHRENIA (2017)

Article Pharmacology & Pharmacy

Characterization of signal bias at the GLP-1 receptor induced by backbone modification of GLP-1

Marlies V. Hager et al.

BIOCHEMICAL PHARMACOLOGY (2017)

Review Developmental Biology

Developmental specification of forebrain cholinergic neurons

Kathryn C. Allaway et al.

DEVELOPMENTAL BIOLOGY (2017)

Article Biochemistry & Molecular Biology

Novel Fused Arylpyrimidinone Based Allosteric Modulators of the M1 Muscarinic Acetylcholine Receptor

Shailesh N. Mistry et al.

ACS CHEMICAL NEUROSCIENCE (2016)

Article Chemistry, Medicinal

Design and optimization of selective azaindole amide M1 positive allosteric modulators

Jennifer E. Davoren et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2016)

Article Chemistry, Medicinal

Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration

Joseph D. Panarese et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2016)

Article Multidisciplinary Sciences

Crystal structures of the M1 and M4 muscarinic acetylcholine receptors

David M. Thal et al.

NATURE (2016)

Review Neurosciences

DREADDs for Neuroscientists

Bryan L. Roth

NEURON (2016)

Article Biochemistry & Molecular Biology

G-protein-coupled receptors mediate 14-3-3 signal transduction

Hua Li et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2016)

Article Pharmacology & Pharmacy

Positive Allosteric Modulation of the Muscarinic M1 Receptor Improves Efficacy of Antipsychotics in Mouse Glutamatergic Deficit Models of Behavior

Kwok H. C. Choy et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2016)

Article Pharmacology & Pharmacy

Molecular Mechanisms of Action of M5 Muscarinic Acetylcholine Receptor Allosteric Modulators

Alice E. Berizzi et al.

MOLECULAR PHARMACOLOGY (2016)

Article Biochemistry & Molecular Biology

Synthesis and Pharmacological Evaluation of M4 Muscarinic Receptor Positive Allosteric Modulators Derived from VU10004

Tracey Huynh et al.

ACS CHEMICAL NEUROSCIENCE (2015)

Review Pharmacology & Pharmacy

Allosteric modulation of nicotinic acetylcholine receptors

Anna Chatzidaki et al.

BIOCHEMICAL PHARMACOLOGY (2015)

Article Biochemistry & Molecular Biology

Central Cholinergic Neurons Are Rapidly Recruited by Reinforcement Feedback

Balazs Hangya et al.

Article Pharmacology & Pharmacy

The catecholaminergic-cholinergic balance hypothesis of bipolar disorder revisited

Jordy van Enkhuizen et al.

EUROPEAN JOURNAL OF PHARMACOLOGY (2015)

Review Behavioral Sciences

The muscarinic system, cognition and schizophrenia

Sean P. Carruthers et al.

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS (2015)

Article Chemistry, Medicinal

Identification of a methoxynaphthalene scaffold as a core replacement in quinolizidinone amide M1 positive allosteric modulators

Scott D. Kuduk et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2014)

Article Biochemistry & Molecular Biology

Molecular Mechanisms of Bitopic Ligand Engagement with the M1 Muscarinic Acetylcholine Receptor

Peter Keov et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Article Biochemistry & Molecular Biology

Molecular Determinants of Allosteric Modulation at the M1 Muscarinic Acetylcholine Receptor

Alaa Abdul-Ridha et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Article Biochemistry & Molecular Biology

Allosteric Modulation of M1 Muscarinic Acetylcholine Receptor Internalization and Subcellular Trafficking

Holly R. Yeatman et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Review Neurosciences

Muscarinic Signaling in the Brain

Alexander Thiele

ANNUAL REVIEW OF NEUROSCIENCE, VOL 36 (2013)

Article Chemistry, Medicinal

Probing Structural Requirements of Positive Allosteric Modulators of the M4 Muscarinic Receptor

Tracey Huynh et al.

JOURNAL OF MEDICINAL CHEMISTRY (2013)

Review Neurosciences

β-Arrestins as Potential Therapeutic Targets for Alzheimer's Disease

Teng Jiang et al.

MOLECULAR NEUROBIOLOGY (2013)

Article Multidisciplinary Sciences

Activation and allosteric modulation of a muscarinic acetylcholine receptor

Andrew C. Kruse et al.

NATURE (2013)

Article Biochemistry & Molecular Biology

beta-arrestin 2 regulates A beta generation and gamma-secretase activity in Alzheimer's disease

Amantha Thathiah et al.

NATURE MEDICINE (2013)

Article Biotechnology & Applied Microbiology

OPINION Signalling bias in new drug discovery: detection, quantification and therapeutic impact

Terry Kenakin et al.

NATURE REVIEWS DRUG DISCOVERY (2013)

Review Biotechnology & Applied Microbiology

Emerging paradigms in GPCR allostery: implications for drug discovery

Denise Wootten et al.

NATURE REVIEWS DRUG DISCOVERY (2013)

Article Neurosciences

Uncoupling of M1 muscarinic receptor/G-protein interaction by amyloid β1-42

Helena Janickova et al.

NEUROPHARMACOLOGY (2013)

Article Pharmacology & Pharmacy

Allosteric Modulation of a Chemogenetically Modified G Protein-Coupled Receptor

Alaa Abdul-Ridha et al.

MOLECULAR PHARMACOLOGY (2013)

Article Pharmacology & Pharmacy

Differential Activation and Modulation of the Glucagon-Like Peptide-1 Receptor by Small Molecule Ligands

Denise Wootten et al.

MOLECULAR PHARMACOLOGY (2013)

Article Biochemistry & Molecular Biology

A Simple Method for Quantifying Functional Selectivity and Agonist Bias

Terry Kenakin et al.

ACS CHEMICAL NEUROSCIENCE (2012)

Article Pharmacology & Pharmacy

Biased signalling and allosteric machines: new vistas and challenges for drug discovery

Terry P. Kenakin

BRITISH JOURNAL OF PHARMACOLOGY (2012)

Article Developmental Biology

Development of Hyperactivity and Anxiety Responses in Dopamine Transporter-Deficient Mice

Alex C. Carpenter et al.

DEVELOPMENTAL NEUROSCIENCE (2012)

Article Biochemistry & Molecular Biology

A Monod-Wyman-Changeux Mechanism Can Explain G Protein-coupled Receptor (GPCR) Allosteric Modulation

Meritxell Canals et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

Article Multidisciplinary Sciences

Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist

Kazuko Haga et al.

NATURE (2012)

Article Medicine, Research & Experimental

Functional Neuroanatomy of the Basal Ganglia

Jose L. Lanciego et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2012)

Article Neurosciences

Functional significance of M-type potassium channels in nociceptive cutaneous sensory endings

Gayle M. Passmore et al.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2012)

Review Neurosciences

AKT/GSK3 signaling pathway and schizophrenia

Effat S. Emamian

FRONTIERS IN MOLECULAR NEUROSCIENCE (2012)

Article Pharmacology & Pharmacy

Allosteric Modulation of Endogenous Metabolites as an Avenue for Drug Discovery

Denise Wootten et al.

MOLECULAR PHARMACOLOGY (2012)

Article Pathology

Loss of Muscarinic M1 Receptor Exacerbates Alzheimer's Disease-Like Pathology and Cognitive Decline

Rodrigo Medeiros et al.

AMERICAN JOURNAL OF PATHOLOGY (2011)

Article Biochemical Research Methods

Muscarinic receptor family interacting proteins: Role in receptor function

Dasiel O. Borroto-Escuela et al.

JOURNAL OF NEUROSCIENCE METHODS (2011)

Article Pharmacology & Pharmacy

Quantifying Ligand Bias at Seven-Transmembrane Receptors

Sudarshan Rajagopal et al.

MOLECULAR PHARMACOLOGY (2011)

Review Neurosciences

The role of G protein-coupled receptors in the pathology of Alzheimer's disease

Amantha Thathiah et al.

NATURE REVIEWS NEUROSCIENCE (2011)

Article Geriatrics & Gerontology

RACK1 is involved in β-amyloid impairment of muscarinic regulation of GABAergic transmission

Wenhua Liu et al.

NEUROBIOLOGY OF AGING (2011)

Article Chemistry, Medicinal

Effects of Conformational Restriction of 2-Amino-3-benzoylthiophenes on A1 Adenosine Receptor Modulation

Luigi Aurelio et al.

JOURNAL OF MEDICINAL CHEMISTRY (2010)

Article Biochemistry & Molecular Biology

Interaction with AKAP79 Modifies the Cellular Pharmacology of PKC

Naoto Hoshi et al.

MOLECULAR CELL (2010)

Review Pharmacology & Pharmacy

Signaling pathways in schizophrenia: emerging targets and therapeutic strategies

Caline S. Karam et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2010)

Article Chemistry, Medicinal

Quinolizidinone Carboxylic Acids as CNS Penetrant, Selective M1 Allosteric Muscarinic Receptor Modulators

Scott D. Kuduk et al.

ACS MEDICINAL CHEMISTRY LETTERS (2010)

Article Pharmacology & Pharmacy

Structural and functional diversity of native brain neuronal nicotinic receptors

Cecilia Gotti et al.

BIOCHEMICAL PHARMACOLOGY (2009)

Article Biochemistry & Molecular Biology

How Does Arrestin Assemble MAPKs into a Signaling Complex?

Xiufeng Song et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

Article Pharmacology & Pharmacy

Selectivity of Agonists for the Active State of M-1 to M-4 Muscarinic Receptor Subtypes

Katherine W. Figueroa et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2009)

Article Biochemistry & Molecular Biology

Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia

E. Scarr et al.

MOLECULAR PSYCHIATRY (2009)

Review Biochemistry & Molecular Biology

Regulation and Physiological Functions of G12/13-Mediated Signaling Pathways

Nobuchika Suzuki et al.

NEUROSIGNALS (2009)

Article Multidisciplinary Sciences

Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation

Lei Ma et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

Article Multidisciplinary Sciences

Regulation of amygdalar PKA by β-arrestin-2/phosphodiesterase-4 complex is critical for fear conditioning

Yuting Li et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

Article Pharmacology & Pharmacy

Differential regulation of muscarinic M1 receptors by orthosteric and allosteric ligands

Christopher N Davis et al.

BMC Pharmacology & Toxicology (2009)

Article Psychiatry

Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia

Anantha Shekhar et al.

AMERICAN JOURNAL OF PSYCHIATRY (2008)

Review Biochemistry & Molecular Biology

Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction

F. Amenta et al.

CURRENT MEDICINAL CHEMISTRY (2008)

Article Chemistry, Medicinal

2-aminothienopyridazines as novel adenosine A1 receptor allosteric modulators and antagonists

Gemma N. Ferguson et al.

JOURNAL OF MEDICINAL CHEMISTRY (2008)

Article Pharmacology & Pharmacy

G Protein Coupling and Signaling Pathway Activation by M1 Muscarinic Acetylcholine Receptor Orthosteric and Allosteric Agonists

Rachel L. Thomas et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2008)

Article Neurosciences

Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease

Rene O. Sanchez-Mejia et al.

NATURE NEUROSCIENCE (2008)

Article Pharmacology & Pharmacy

On the analysis of ligand-directed signaling at G protein-coupled receptors

Frederick J. Ehlert

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY (2008)

Article Behavioral Sciences

Transfection of mutant CREB in the striatum, but not the hippocampus, impairs long-term memory for response learning

Jennifer J. Brightwell et al.

NEUROBIOLOGY OF LEARNING AND MEMORY (2008)

Review Pharmacology & Pharmacy

Muscarinic acetylcholine receptors as CNS drug targets

Christopher J. Langmead et al.

PHARMACOLOGY & THERAPEUTICS (2008)

Article Multidisciplinary Sciences

Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia

W. Y. Chan et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

Review Biochemistry & Molecular Biology

Current therapeutic options for Alzheimer's disease

Alberto Lleo

CURRENT GENOMICS (2007)

Review Pharmacology & Pharmacy

Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology

Katie Leach et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2007)

Review Biochemistry & Molecular Biology

Towards a muscarinic hypothesis of schizophrenia

T. J. Raedler et al.

MOLECULAR PSYCHIATRY (2007)

Article Pharmacology & Pharmacy

Genetic deletion of muscarinic M4 receptors is anxiolytic in the shock-probe burying model

A Degroot et al.

EUROPEAN JOURNAL OF PHARMACOLOGY (2006)

Review Biochemistry & Molecular Biology

Subtyping schizophrenia: implications for genetic research

A. Jablensky

MOLECULAR PSYCHIATRY (2006)

Article Pharmacology & Pharmacy

Allosteric modulation of the cannabinoid CB1 receptor

MR Price et al.

MOLECULAR PHARMACOLOGY (2005)

Article Genetics & Heredity

Convergent evidence for impaired AKT1-GSK3β signaling in schizophrenia

ES Emamian et al.

NATURE GENETICS (2004)

Article Biochemistry & Molecular Biology

ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic receptor

R Mitchell et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2003)

Article Clinical Neurology

Role of protein kinase B in Alzheimer's neurofibrillary pathology

JJ Pei et al.

ACTA NEUROPATHOLOGICA (2003)

Article Biochemistry & Molecular Biology

M-1 muscarinic agonists can modulate some of the hallmarks in Alzheimer's disease - Implications in future therapy

A Fisher et al.

JOURNAL OF MOLECULAR NEUROSCIENCE (2003)

Article Neurosciences

M1 muscarinic receptor signaling in mouse hippocampus and cortex

AC Porter et al.

BRAIN RESEARCH (2002)

Review Pharmacology & Pharmacy

G protein-coupled receptor allosterism and complexing

A Christopoulos et al.

PHARMACOLOGICAL REVIEWS (2002)

Article Multidisciplinary Sciences

Hyperactivity, elevated dopaminergic transmission, and response to amphetamine in M1 muscarinic acetylcholine receptor-deficient mice

DJ Gerber et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001)

Article Biochemistry & Molecular Biology

The M1 receptor is required for muscarinic activation of mitogen-activated protein (MAP) kinase in murine cerebral cortical neurons

SE Hamilton et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2001)

Article Biochemistry & Molecular Biology

Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia

K Mirnics et al.

MOLECULAR PSYCHIATRY (2001)