Opioid receptor targeting ligands for pain management: a review and update

Abstract

Importance of the field: Discovery and synthesis of analgesic ligands can potentially improve analgesia, reduce side effects, minimize psychologic dependence and delay analgesic tolerance.

Areas covered in this review: This review covers opioid peptides and analogs and bifunctional opioid ligands, and bifunctional opioid/non-opioid ligands as new, potentially useful analgesics. Several lines of investigation have resulted in potentially useful agents.

What the reader will gain: Modifications of peptide structures have improved opioid receptor affinity, efficacy, stability, half-life and CNS penetrations. Opioid μ receptor agonists have been used to form multi-targeted directed ligands (MDL), which in animal models improve the therapeutic index of the analgesic relative to monovalent potent μ receptor agents. These new opioid ligands are reviewed in detail.

Take home message: Modified opioid peptides and MDL ligands are potentially better analgesics than morphine.

Keywords::

• bifunctional
• ligand
• opioid
• pharmacophore

Acknowledgments

The author wishes to thank M Wells and C Cernanec for preparing this manuscript.

Notes

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