title: Opioid receptor targeting ligands for pain management: a review and update.
abstract: BACKGROUND
  Discovery and synthesis of analgesic ligands can potentially improve analgesia, reduce side effects, minimize psychologic dependence and delay analgesic tolerance.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Modified opioid peptides and MDL ligands are potentially better analgesics than morphine.
authors: Department of Solid Tumor Oncology, The Harry R. Horvitz Center for Palliative Medicine, Taussig Cancer Institute, 9500 Euclid Avenue R35, Cleveland, OH 44195, USA  +1 216 444 7793 ;  +1 216 636 3179 ;  davism6@ccf.org.
authors: Mellar P
authors: MP
authors: Davis