Multifunctional Opioid Ligands

2018 ◽  
pp. 21-51 ◽  
Author(s):  
Jessica P. Anand ◽  
Deanna Montgomery
Keyword(s):  
Opioid Ligands

Multitarget Opioid/Non-opioid Ligands: A Potential Approach in Pain Management

2016 ◽  
Vol 23 (40) ◽  
pp. 4506-4528 ◽  
Author(s):  
Rita Turnaturi ◽  
Giuseppina Arico ◽  
Giuseppe Ronsisvalle ◽  
Lorella Pasquinucci ◽  
Carmela Parenti
Keyword(s):  
Pain Management ◽  
Potential Approach ◽  
Opioid Ligands

scholarly journals Biased ligands at opioid receptors: Current status and future directions

2021 ◽  
Vol 14 (677) ◽  
pp. eaav0320
Author(s):  
Tao Che ◽  
Hemlata Dwivedi-Agnihotri ◽  
Arun K. Shukla ◽  
Bryan L. Roth
Keyword(s):  
Opioid Receptors ◽  
Current Status ◽  
Functional Responses ◽  
Future Directions ◽  
Health Crisis ◽  
Biased Agonism ◽  
Opioid Ligands ◽  
Therapeutic Benefits ◽  
Ligand Discovery ◽  
Opioid Medications

The opioid crisis represents a major worldwide public health crisis that has accelerated the search for safer and more effective opioids. Over the past few years, the identification of biased opioid ligands capable of eliciting selective functional responses has provided an alternative avenue to develop novel therapeutics without the side effects of current opioid medications. However, whether biased agonism or other pharmacological properties, such as partial agonism (or low efficacy), account for the therapeutic benefits remains questionable. Here, we provide a summary of the current status of biased opioid ligands that target the μ- and κ-opioid receptors and highlight advances in preclinical and clinical trials of some of these ligands. We also discuss an example of structure-based biased ligand discovery at the μ-opioid receptor, an approach that could revolutionize drug discovery at opioid and other receptors. Last, we briefly discuss caveats and future directions for this important area of research.

Label-free cell phenotypic study of opioid receptors and discovery of novel mu opioid ligands from natural products

2021 ◽  
Vol 270 ◽  
pp. 113872
Author(s):  
Tao Hou ◽  
Fangfang Xu ◽  
Xingrong Peng ◽  
Han Zhou ◽  
Xiuli Zhang ◽  
...  
Keyword(s):  
Natural Products ◽  
Opioid Receptors ◽  
Free Cell ◽  
Label Free ◽  
Mu Opioid ◽  
Opioid Ligands

Differential depressive action of two μ and δ opioid ligands on neuronal responses to noxious stimuli in the thalamic ventrobasal complex of rat

1986 ◽  
Vol 398 (1) ◽  
pp. 49-56 ◽  
Author(s):  
J.M. Benoist ◽  
V. Kayser ◽  
G. Gacel ◽  
J.M. Zajac ◽  
M. Gautron ◽  
...  
Keyword(s):  
Neuronal Responses ◽  
Opioid Ligands ◽  
Ventrobasal Complex ◽  
Noxious Stimuli

ChemInform Abstract: Multitarget Opioid Ligands in Pain Relief: New Players in an Old Game

ChemInform ◽  
2016 ◽  
Vol 47 (12) ◽  
pp. no-no
Author(s):  
Rita Turnaturi ◽  
Giuseppina Arico ◽  
Giuseppe Ronsisvalle ◽  
Carmela Parenti ◽  
Lorella Pasquinucci
Keyword(s):  
Pain Relief ◽  
Opioid Ligands

ChemInform Abstract: Design and Synthesis of Novel Opioid Ligands and Their Pharmacologies

ChemInform ◽  
2012 ◽  
Vol 43 (45) ◽  
pp. no-no
Author(s):  
Hiroshi Nagase ◽  
Hideaki Fujii
Keyword(s):  
Opioid Ligands ◽  
Design And Synthesis

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

2020 ◽  
Vol 13 (625) ◽  
pp. eaaz3140 ◽  
Author(s):  
Alexander Gillis ◽  
Arisbel B. Gondin ◽  
Andrea Kliewer ◽  
Julie Sanchez ◽  
Herman D. Lim ◽  
...  
Keyword(s):  
G Protein ◽  
Side Effect ◽  
Opioid Analgesics ◽  
Receptor Activation ◽  
Alternative Mechanism ◽  
Protein Activation ◽  
Biased Agonism ◽  
Opioid Ligands ◽  
Intrinsic Efficacy ◽  
Respiratory Depressant

Biased agonism at G protein–coupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement of G proteins versus β-arrestins are commonly limited by the small response windows obtained in pathways that are not amplified or are less effectively coupled to receptor engagement, such as β-arrestin recruitment. At the μ-opioid receptor (MOR), G protein–biased ligands have been proposed to induce less constipation and respiratory depressant side effects than opioids commonly used to treat pain. However, it is unclear whether these improved safety profiles are due to a reduction in β-arrestin–mediated signaling or, alternatively, to their low intrinsic efficacy in all signaling pathways. Here, we systematically evaluated the most recent and promising MOR-biased ligands and assessed their pharmacological profile against existing opioid analgesics in assays not confounded by limited signal windows. We found that oliceridine, PZM21, and SR-17018 had low intrinsic efficacy. We also demonstrated a strong correlation between measures of efficacy for receptor activation, G protein coupling, and β-arrestin recruitment for all tested ligands. By measuring the antinociceptive and respiratory depressant effects of these ligands, we showed that the low intrinsic efficacy of opioid ligands can explain an improved side effect profile. Our results suggest a possible alternative mechanism underlying the improved therapeutic windows described for new opioid ligands, which should be taken into account for future descriptions of ligand action at this important therapeutic target.

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