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

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.