scholarly journals Critical Assessment of G Protein-Biased Agonism at the μ-Opioid Receptor

2020 ◽  
Vol 41 (12) ◽  
pp. 947-959 ◽  
Author(s):  
Alexander Gillis ◽  
Andrea Kliewer ◽  
Eamonn Kelly ◽  
Graeme Henderson ◽  
Macdonald J. Christie ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Critical Assessment ◽  
Biased Agonism ◽  
Μ Opioid Receptor

scholarly journals Comparison of an Addictive Potential of μ-Opioid Receptor Agonists with G Protein Bias: Behavioral and Molecular Modeling Studies

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 55
Author(s):  
Lucja Kudla ◽  
Ryszard Bugno ◽  
Sabina Podlewska ◽  
Lukasz Szumiec ◽  
Lucja Wiktorowska ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Physical Dependence ◽  
Behavioral Effects ◽  
Morphine Dependence ◽  
Biased Agonism ◽  
Receptor Agonists ◽  
Μ Opioid Receptor ◽  
Antinociceptive Tolerance ◽  
Opioid Receptor Agonists

Among different approaches to the search for novel—safer and less addictive—opioid analgesics, biased agonism has received the most attention in recent years. Some μ-opioid receptor agonists with G protein bias, including SR compounds, were proposed to induce diminished side effects. However, in many aspects, behavioral effects of those compounds, as well as the mechanisms underlying differences in their action, remain unexplored. Here, we aimed to evaluate the effects of SR-14968 and SR-17018, highly G protein-biased opioid agonists, on antinociception, motor activity and addiction-like behaviors in C57BL/6J mice. The obtained results showed that the compounds induce strong and dose-dependent antinociception. SR-14968 causes high, and SR-17018 much lower, locomotor activity. Both agonists develop reward-associated behavior and physical dependence. The compounds also cause antinociceptive tolerance, however, developing more slowly when compared to morphine. Interestingly, SR compounds, in particular SR-17018, slow down the development of antinociceptive tolerance to morphine and inhibit some symptoms of morphine withdrawal. Therefore, our results indicate that SR agonists possess rewarding and addictive properties, but can positively modulate some symptoms of morphine dependence. Next, we have compared behavioral effects of SR-compounds and PZM21 and searched for a relationship to the substantial differences in molecular interactions that these compounds form with the µ-opioid receptor.

A First‐in‐Human Clinical Study With TRV734, an Orally Bioavailable G‐Protein–Biased Ligand at the μ‐Opioid Receptor

2019 ◽  
Vol 9 (2) ◽  
pp. 256-266 ◽  
Author(s):  
Ian E. James ◽  
Franck Skobieranda ◽  
David G. Soergel ◽  
Kimberly A. Ramos ◽  
Dennis Ruff ◽  
...  
Keyword(s):  
Clinical Study ◽  
G Protein ◽  
Opioid Receptor ◽  
Μ Opioid Receptor ◽  
Orally Bioavailable ◽  
Human Clinical Study

scholarly journals A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal

2019 ◽  
Vol 45 (2) ◽  
pp. 416-425 ◽  
Author(s):  
Travis W. Grim ◽  
Cullen L. Schmid ◽  
Edward L. Stahl ◽  
Fani Pantouli ◽  
Jo-Hao Ho ◽  
...  
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Morphine Tolerance ◽  
Morphine Withdrawal ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Μ Opioid Receptor ◽  
Biased Agonist

scholarly journals Pharmacological Characters of Oliceridine, a μ-Opioid Receptor G-Protein–Biased Ligand in Mice

2019 ◽  
Vol 129 (5) ◽  
pp. 1414-1421 ◽  
Author(s):  
De-Yong Liang ◽  
Wen-Wu Li ◽  
Chinwe Nwaneshiudu ◽  
Karen-Amanda Irvine ◽  
J. David Clark
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
Μ Opioid Receptor

scholarly journals Absence of G-protein activation by μ-opioid receptor agonists in the spinal cord of μ-opioid receptor knockout mice

1999 ◽  
Vol 126 (2) ◽  
pp. 451-456 ◽  
Author(s):  
Minoru Narita ◽  
Hirokazu Mizoguchi ◽  
Michiko Narita ◽  
Ichiro Sora ◽  
George R Uhl ◽  
...  
Keyword(s):  
Spinal Cord ◽  
G Protein ◽  
Opioid Receptor ◽  
Knockout Mice ◽  
Protein Activation ◽  
Receptor Agonists ◽  
G Protein Activation ◽  
Μ Opioid Receptor ◽  
Opioid Receptor Agonists

scholarly journals Live Cell Monitoring of μ-Opioid Receptor-mediated G-protein Activation Reveals Strong Biological Activity of Close Morphine Biosynthetic Precursors

2007 ◽  
Vol 282 (37) ◽  
pp. 27126-27132 ◽  
Author(s):  
Viacheslav O. Nikolaev ◽  
Chotima Boettcher ◽  
Christian Dees ◽  
Moritz Bünemann ◽  
Martin J. Lohse ◽  
...  
Keyword(s):  
Biological Activity ◽  
G Protein ◽  
Opioid Receptor ◽  
Live Cell ◽  
Protein Activation ◽  
G Protein Activation ◽  
Cell Monitoring ◽  
Μ Opioid Receptor

scholarly journals Selective Interference of β-Arrestin 1 with κ and δ but Not μ Opioid Receptor/G Protein Coupling

1998 ◽  
Vol 273 (38) ◽  
pp. 24328-24333 ◽  
Author(s):  
Zhi-Jie Cheng ◽  
Qing-Ming Yu ◽  
Ya-Lan Wu ◽  
Lan Ma ◽  
Gang Pei
Keyword(s):  
G Protein ◽  
Opioid Receptor ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Selective Interference ◽  
Μ Opioid Receptor
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