title: Pharmacological traits of delta opioid receptors: pitfalls or opportunities?
abstract: BACKGROUND
  Delta opioid receptors (DORs) have been considered as a potential target to relieve pain as well as treat depression and anxiety disorders and are known to modulate other physiological responses, including ethanol and food consumption. A small number of DOR-selective drugs are in clinical trials, but no DOR-selective drugs have been approved by the Federal Drug Administration and some candidates have failed in phase II clinical trials, highlighting current difficulties producing effective delta opioid-based therapies. Recent studies have provided new insights into the pharmacology of the DOR, which is often complex and at times paradoxical.
  
  
  OBJECTIVE
  This review will discuss the existing literature focusing on four aspects: (1) Two DOR subtypes have been postulated based on differences in pharmacological effects of existing DOR-selective ligands. (2) DORs are expressed ubiquitously throughout the body and central nervous system and are, thus, positioned to play a role in a multitude of diseases. (3) DOR expression is often dynamic, with many reports of increased expression during exposure to chronic stimuli, such as stress, inflammation, neuropathy, morphine, or changes in endogenous opioid tone. (4) A large structural variety in DOR ligands implies potential different mechanisms of activating the receptor.
  
  
  CONCLUSIONS
  The reviewed features of DOR pharmacology illustrate the potential benefit of designing tailored or biased DOR ligands.
authors: Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton St., Suite 200, Emeryville, CA 94608, USA. rvanrijn@gallo.ucsf.edu
authors: Richard M
authors: RM
authors: van Rijn
authors: Julia N
authors: JN
authors: Defriel
authors: Jennifer L
authors: JL
authors: Whistler
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002986:Clinical Trials as Topic; D015195:Drug Design; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D017465:Receptors, Opioid, delta / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D008024:Ligands; D017465:Receptors, Opioid, delta
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