title: The emerging therapeutic roles of κ-opioid agonists.
abstract: The current practice of μ-opioid receptor agonists such as morphine as the primary means of acute and chronic pain relief has several dangerous consequences that limit their effectiveness, including respiratory depression, gastrointestinal motility inhibition, addiction, tolerance, and abuse. Several other opioid receptors, notably the μ-opioid (KOP) receptor, have long been known to play a role in pain relief. Recent discoveries and advancements in laboratory techniques have allowed significant developments of KOP agonists as potential novel therapies for pain relief and other pathological processes. These drugs exhibit none of the classic opioid adverse effects and have displayed pronounced analgesia in several different scenarios. New formulations since 2014 have unveiled increased oral bioavailability, exceptional peripheral versus central selectivity, and a positive safety profile. Continued refinements of established μ-opioid agonist formulations have virtually eliminated the centrally mediated side effects of dysphoria and sedation that limited the applicability of previous KOP agonists. Further research is required to better elucidate the potential of these compounds in pain management, as well as in the mediation or modulation of other complex pathophysiological processes as therapeutic agents.
authors.affiliation: Medical Student, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Jones
authors.affiliation: Professor and Chairman, Department of Anesthesiology, LSU School of Medicine, New Orleans, Louisiana.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Kaye
authors.affiliation: Medical Student, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Kaye
authors.affiliation: Associate Professor, Harvard Medical School, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Urman
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D009293:Opioid-Related Disorders / Q000517:prevention & control; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D017473:Receptors, Opioid, kappa