Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists

Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects

(2019) A. Kliewer et al.   Nature Communications

APOLLO-1: a randomized placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the µ-opioid receptor, for management of moderate-to-severe acute pain following bunionectomy

(2019) Eugene R Viscusi et al.   Journal of Pain Research

A biased view of µ opioid receptors?

(2019) Alexandra E Conibear et al.   MOLECULAR PHARMACOLOGY

Biased agonism of clinically approved μ-opioid receptor agonists and TRV130 is not controlled by binding and signaling kinetics

(2019) Mie Fabricius Pedersen et al.   NEUROPHARMACOLOGY

APOLLO ‐2: A Randomized, Placebo and Active‐Controlled Phase III Study Investigating Oliceridine ( TRV 130), a G Protein‐Biased Ligand at the μ‐Opioid Receptor, for Management of Moderate to Severe Acute Pain Following Abdominoplasty

(2019) Neil K. Singla et al.   Pain Practice

A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor

(2019) Zoltan Dekan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Exploring use of unsupervised clustering to associate signaling profiles of GPCR ligands to clinical response

(2019) Besma Benredjem et al.   Nature Communications

The novel μ-opioid receptor agonist PZM21 depresses respiration and induces tolerance to antinociception

(2018) Rob Hill et al.   BRITISH JOURNAL OF PHARMACOLOGY

Mini G protein probes for active G protein–coupled receptors (GPCRs) in live cells

(2018) Qingwen Wan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A Genetically Encoded Biosensor Reveals Location Bias of Opioid Drug Action

(2018) Miriam Stoeber et al.   NEURON

Progress in understanding mechanisms of opioid-induced gastrointestinal adverse effects and respiratory depression

(2018) Mohammad Zafar Imam et al.   NEUROPHARMACOLOGY

Multisite phosphorylation is required for sustained interaction with GRKs and arrestins during rapid μ-opioid receptor desensitization

(2018) Elke Miess et al.   Science Signaling

Multisite phosphorylation is required for sustained interaction with GRKs and arrestins during rapid μ-opioid receptor desensitization

(2018) Elke Miess et al.   Science Signaling

The G-protein biased mu-opioid agonist, TRV130, produces reinforcing and antinociceptive effects that are comparable to oxycodone in rats

(2018) C. Austin Zamarripa et al.   DRUG AND ALCOHOL DEPENDENCE

When trafficking and signaling mix: how subcellular location shapes GPCR activation of heterotrimeric G proteins

(2018) Braden T. Lobingier et al.   TRAFFIC

Effects of acute and repeated treatment with the biased mu opioid receptor agonist TRV130 (oliceridine) on measures of antinociception, gastrointestinal function, and abuse liability in rodents

(2017) Ahmad A Altarifi et al.   JOURNAL OF PSYCHOPHARMACOLOGY

A Complementary Scale of Biased Agonism for Agonists with Differing Maximal Responses

(2017) Javier Burgueño et al.   Scientific Reports

A randomized, Phase IIb study investigating oliceridine (TRV130), a novel µ-receptor G-protein pathway selective (µ-GPS) modulator, for the management of moderate to severe acute pain following abdominoplasty

(2017) Neil Singla et al.   Journal of Pain Research

G-protein–gated Inwardly Rectifying Potassium Channels Modulate Respiratory Depression by Opioids

(2016) Gaspard Montandon et al.   ANESTHESIOLOGY

Systematic analysis of factors influencing observations of biased agonism at the mu-opioid receptor

(2016) Georgina L. Thompson et al.   BIOCHEMICAL PHARMACOLOGY

Structure-based discovery of opioid analgesics with reduced side effects

(2016) Aashish Manglik et al.   NATURE

The role of kinetic context in apparent biased agonism at GPCRs

(2016) Carmen Klein Herenbrink et al.   Nature Communications

μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive

(2015) Erica S. Levitt et al.   JOURNAL OF PHYSIOLOGY-LONDON

A Comparision of Nalbuphine with Morphine for Analgesic Effects and Safety : Meta-Analysis of Randomized Controlled Trials

(2015) Zheng Zeng et al.   Scientific Reports

The clinical analgesic efficacy of buprenorphine

(2014) R. B. Raffa et al.   JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS

Disruption of the Na+ion binding site as a mechanism for positive allosteric modulation of the mu-opioid receptor

(2014) Kathryn E. Livingston et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Biased ligands at G-protein-coupled receptors: promise and progress

(2014) Jonathan D. Violin et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Ligand bias at the μ-opioid receptor

(2013) Eamonn Kelly   BIOCHEMICAL SOCIETY TRANSACTIONS

Efficacy and ligand bias at the μ-opioid receptor

(2013) E Kelly   BRITISH JOURNAL OF PHARMACOLOGY

μ-Opioid receptor activation and noradrenaline transport inhibition by tapentadol in rat single locus coeruleus neurons

(2013) Mahsa Sadeghi et al.   BRITISH JOURNAL OF PHARMACOLOGY

Measurements of ligand bias and functional affinity

(2013) Terry Kenakin et al.   NATURE REVIEWS DRUG DISCOVERY

Respiratory toxicity of buprenorphine results from the blockage of P-glycoprotein-mediated efflux of norbuprenorphine at the blood–brain barrier in mice

(2012) Hisham Alhaddad et al.   CRITICAL CARE MEDICINE

Systematic review of efficacy and safety of buprenorphine versus fentanyl or morphine in patients with chronic moderate to severe pain

(2012) Robert F. Wolff et al.   CURRENT MEDICAL RESEARCH AND OPINION

Buprenorphine May Not Be as Safe as You Think: A Pediatric Fatality From Unintentional Exposure

(2012) H. K. Kim et al.   PEDIATRICS

Sensitive and High Resolution Localization and Tracking of Membrane Proteins in Live Cells with BRET

(2012) Tien-Hung Lan et al.   TRAFFIC

A Simple Method for Quantifying Functional Selectivity and Agonist Bias

(2011) Terry Kenakin et al.   ACS Chemical Neuroscience

Buprenorphine Metabolites, Buprenorphine-3-glucuronide and Norbuprenorphine-3-glucuronide, Are Biologically Active

(2011) Sarah M. Brown et al.   ANESTHESIOLOGY

Quantifying Ligand Bias at Seven-Transmembrane Receptors

(2011) S. Rajagopal et al.   MOLECULAR PHARMACOLOGY

 -Opioid Receptors: Correlation of Agonist Efficacy for Signalling with Ability to Activate Internalization

(2010) J. McPherson et al.   MOLECULAR PHARMACOLOGY

Current Knowledge of Buprenorphine and Its Unique Pharmacological Profile

(2010) Joseph Pergolizzi et al.   Pain Practice

Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine

(2008) Hans G. Kress   EUROPEAN JOURNAL OF PAIN