A Novel Method for Analyzing Extremely Biased Agonism at G Protein–Coupled Receptors

No abstract is available for this paper.

• Publication year

  2015

• Venue

  Molecular Pharmacology

• Publication date

  2015-05-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1124/mol.114.096503PMID 25680753PMCID PMC4407734
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Measurements of ligand bias and functional affinity

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  2013influential reference
• A G Protein-Biased Ligand at the μ-Opioid Receptor Is Potently Analgesic with Reduced Gastrointestinal and Respiratory Dysfunction Compared with Morphine

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• Development of Functionally Selective, Small Molecule Agonists at Kappa Opioid Receptors*

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

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• 6′-Guanidinonaltrindole (6′-GNTI) Is a G Protein-biased κ-Opioid Receptor Agonist That Inhibits Arrestin Recruitment*

  2012influential reference
• A simple method for quantifying functional selectivity and agonist bias.

  2012influential reference
• Functional Selectivity and Biased Receptor Signaling

  2011cited by this paper
• Quantifying Ligand Bias at Seven-Transmembrane Receptors

  2011influential reference
• Seeking ligand bias: assessing GPCR coupling to β-arrestins for drug discovery.

  2010cited by this paper
• Seeking Ligand Bias: Assessing GPCR Coupling to Beta-Arrestins for Drug Discovery.

  2010cited by this paper
• Estimation of Relative Microscopic Affinity Constants of Agonists for the Active State of the Receptor in Functional Studies on M2 and M3 Muscarinic Receptors

  2009cited by this paper
• Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system

  2008cited by this paper
• The Dysphoric Component of Stress Is Encoded by Activation of the Dynorphin κ-Opioid System

  2008cited by this paper
• On the analysis of ligand-directed signaling at G protein-coupled receptors

  2008cited by this paper
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  2008cited by this paper
• Pharmacological Evidence for a Motivational Role of κ-Opioid Systems in Ethanol Dependence

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• Functional Selectivity and Classical Concepts of Quantitative Pharmacology

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• Kappa Opioid Receptor Activation of p38 MAPK Is GRK3- and Arrestin-dependent in Neurons and Astrocytes*

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  2004cited by this paper
• Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist.

  2004cited by this paper
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  2004cited by this paper
• Principles: receptor theory in pharmacology.

  2004cited by this paper
• Ligand-selective receptor conformations revisited: the promise and the problem.

  2003cited by this paper
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  2002cited by this paper
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• A simple method for estimation of agonist activity at receptor subtypes: comparison of native and cloned M3 muscarinic receptors in guinea pig ileum and transfected cells.

  1999cited by this paper
• Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus.

  1998influential reference
• A three-state receptor model of agonist action.

  1997cited by this paper
• A novel mechanism of activity‐dependent NMDA receptor antagonism describes the effect of ifenprodil in rat cultured cortical neurones.

  1996cited by this paper
• The two-state model of receptor activation.

  1995cited by this paper
• Agonist-receptor efficacy. II. Agonist trafficking of receptor signals.

  1995cited by this paper
• A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence.

  1994cited by this paper
• Psychotomimesis mediated by kappa opiate receptors

  1986cited by this paper
• Operational models of pharmacological agonism

  1983cited by this paper
• Narcotic antagonists. 4. Carbon-6 derivatives of N-substituted noroxymorphones as narcotic antagonists.

  1975cited by this paper
• ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.

  1965cited by this paper
• Interaction at end-plate receptors between different choline derivatives

  1957cited by this paper
• The journal of pharmacology and experimental therapeutics

  year unknowncited by this paper

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  2023cites this paper
• Community guidelines for GPCR ligand bias: IUPHAR review 32

  2022cites this paper
• Biased Agonism: Lessons from Studies of Opioid Receptor Agonists.

  2022cites this paper
• A systematic review on the kappa opioid receptor and its ligands: New directions for the treatment of pain, anxiety, depression, and drug abuse.

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