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

@article{Imam2018ProgressIU,
  title={Progress in understanding mechanisms of opioid-induced gastrointestinal adverse effects and respiratory depression},
  author={Mohammad Zafar Imam and Andy Kuo and Sussan Ghassabian and Maree T. Smith},
  journal={Neuropharmacology},
  year={2018},
  volume={131},
  pages={238-255}
}

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References

SHOWING 1-10 OF 333 REFERENCES

Targeting multiple opioid receptors – improved analgesics with reduced side effects?

The main focus of this review is to assess the paradigm of opioid ligands targeting multiple receptors with a single chemical entity and reflect on this rationale by discussing the biological actions of particular multi‐opioid receptor ligands, but not on their medicinal chemistry and design.

Molecular Physiology of Enteric Opioid Receptors

Tolerance develops to the analgesic effects of opioid receptor agonists but not to the constipating actions, due to differential β-arrestin-2-dependent opioid receptor desensitization and internalization in enteric nerves in the colon compared with the small intestine and in neuronal pain pathways.

Functional Selectivity at the μ-Opioid Receptor: Implications for Understanding Opioid Analgesia and Tolerance

This review summarizes both in vitro and in vivo work demonstrating functional selectivity at the μ opioid receptor in terms of G protein coupling, receptor phosphorylation, interactions with β-arrestins, receptor desensitization, internalization and signaling, and details on how these differences may relate to the progression of analgesic tolerance after their extended use.

Opioid receptors in the gastrointestinal tract

  • P. Holzer
  • Biology, Medicine
    Regulatory Peptides
  • 2009

Evidence that opioids may have toll-like receptor 4 and MD-2 effects

Opioid ligands with mixed μ/δ opioid receptor interactions: An emerging approach to novel analgesics

Development of new opioid ligands possessing mixed μ agonist/δ agonist profile and mixed μ receptor agonists as well as δ receptor antagonists profile has emerged as a promising new approach to analgesic drug development.

Molecular mechanisms of opioid receptor-dependent signaling and behavior.

There is a continued need for more translational work on opioid receptors in vivo and the authors put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention.

Physiology, signaling, and pharmacology of opioid receptors and their ligands in the gastrointestinal tract: current concepts and future perspectives

The opportunities of targeting the opioid system are discussed, suggesting future treatment options for functional disorders and inflammatory states of the GI tract.

Non-analgesic effects of opioids: opioid-induced respiratory depression.

A novel approach is aimed at the reduction of respiratory depression from opioid-activation of (micro-)glia cells in the pons and brainstem using micro-glia cell stabilizers which seems an attractive alternative to the classical reversal strategies with naloxone.
...