Distinct Profiles of Desensitization of μ-Opioid Receptors Caused by Remifentanil or Fentanyl: In Vitro Assay with Cells and Three-Dimensional Structural Analyses

Article Anesthesiology

Novel Opioid Analgesics for the Development of Transdermal Opioid Patches That Possess Morphine-Like Pharmacological Profiles Rather Than Fentanyl: Possible Opioid Switching Alternatives Among Patch Formula

Akane Komatsu et al.

Summary: The compounds N1 and N2 have high transdermal absorbability and equivalent analgesic effects as morphine. They may be attractive compounds for the development of novel opioid patches for transitioning from fentanyl patches.

ANESTHESIA AND ANALGESIA (2022)

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Article Biochemistry & Molecular Biology

Ketamine Improves Desensitization of μ-Opioid Receptors Induced by Repeated Treatment with Fentanyl but Not with Morphine

Yusuke Mizobuchi et al.

Summary: This study investigated the effects of ketamine on opioid tolerance and its potential mechanisms. The results showed that ketamine improved acute desensitization and enhanced beta-arrestin recruitment elicited by fentanyl but not by morphine. These effects may involve modulation of GRK-mediated pathways.

BIOMOLECULES (2022)

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Editorial Material Biochemistry & Molecular Biology

Visualizing ligand bias at the Mu-opioid receptor

Catalina A. Zamorano et al.

Summary: In this study, Xu et al. used cryo-EM and computational simulations to investigate how different m-opioid receptor selective-ligands interact with key residues to produce downstream signaling.

CELL (2022)

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Article Biochemistry & Molecular Biology

Molecular recognition of morphine and fentanyl by the human μ-opioid receptor

Youwen Zhuang et al.

Summary: This study reports the structural differences in the binding of morphine and fentanyl to the human mu-opioid receptor (mu OR), as well as the preferential interactions of other agonists with specific regions of the receptor. Mutations at certain regions abolish the recruitment of arrestin by morphine and fentanyl. Ligands designed to reduce interactions with specific regions display preferential G protein signaling. These findings provide crucial insights into the recognition and signaling of fentanyl, which could aid in the rational design of next-generation analgesics.

CELL (2022)

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Article Chemistry, Medicinal

Structural Assessment of Agonist Efficacy in the μ-Opioid Receptor: Morphine and Fentanyl Elicit Different Activation Patterns

Adrian Ricarte et al.

Summary: This study used molecular dynamics simulations to reveal differences in the interactions of fentanyl and morphine with the MOR, highlighting distinct ligand-receptor binding modes and intracellular receptor conformational changes. The observations may provide insights for designing safer but equally effective opioid drugs by understanding the functional variances between fentanyl and morphine.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2021)

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Article Neurosciences

Pharmacological and genetic manipulations at the μ-opioid receptor reveal arrestin-3 engagement limits analgesic tolerance and does not exacerbate respiratory depression in mice

Li He et al.

Summary: Opioid drugs act by activating the mu-opioid receptor to provide analgesic effects, while potentially leading to side effects such as respiratory depression and tolerance development. Recent studies challenge the prevailing hypothesis that arrestin-3 recruitment contributes to respiratory depression and analgesic tolerance, proposing that future development of safer opioids should target ligands that recruit both G protein and arrestin-3.

NEUROPSYCHOPHARMACOLOGY (2021)

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Article Biochemical Research Methods