title: The ORL-1 receptor system: are there opportunities for antagonists in pain therapy?
abstract: Following the cloning of the classical opioid receptors (mu, delta and kappa), the opioid receptor like-1 (ORL-1) was identified as a G-protein coupled receptor (GPCR) with 65% structure homology to the other members of the opioid family. Its endogenous ligand nociception/orphanin FQ (N/OFQ) was discovered shortly thereafter, becoming the subject of investigation in numerous studies. Since activation of the ORL-1 receptor by N/OFQ leads to G alpha(i)-coupling and signal transduction similar to that of opioid receptors, N/OFQ was thought to have a role in pain modulation, similar to that of the endogenous opioids. Surprisingly, studies characterizing N/OFQ's effects on pain transmission yielded conflicting results, attributing to N/OFQ both pronociceptive and antinociceptive actions, depending on doses and routes of administration as well as species and sex of the subjects. With the development of selective and potent ORL-1 antagonists, many scientists believed these contradicting actions would be elucidated. Here we review the recent literature reporting the use of novel ORL-1 antagonists, both peptide and non-peptide, in different models of pain and discuss their use as research tools or potential drug candidates.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Fioravanti
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
mesh_terms: D000818:Animals; D006801:Humans; D009292:Narcotic Antagonists; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: D009292:Narcotic Antagonists; D010455:Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human