title: Systemic and spinal analgesic activity of a delta-opioid-selective lanthionine enkephalin analog.
abstract: A lanthionine enkephalin derivative, Tyr-c[D-Val(L)-Gly-Phe-D-Ala(L)]-OH (DV(L)(2)DA(L)(5)LanEnk), where Val(L) and Ala(L) denote the lanthionine amino acid ends linked via a monosulfide bridge to form the lanthionine structure, was synthesized. It was found to possess selectivity for and potency at the delta versus mu opioid receptor as defined by binding studies and by its respective activity on the mouse vas deferens compared with the guinea pig ileum. The agent produced a potent analgesia after intrathecal and intraperitoneal delivery with ED(50) values being, respectively, 0.19 mucrog and 0.49 mg/kg. The effects of the agent were reversed by the delta-selective antagonist naltrindole. These analgesic actions occurred at doses that had no effect upon general behavior or motor function. These results suggest a potent delta-preferring agent suitable for development as a systemic delta opioid analgesic.
authors.affiliation: Department of Anesthesiology, University of California, San Diego, La Jolla, California 92093-0818, USA.
authors.forename: Camilla I
authors.initials: CI
authors.lastname: Svensson
authors.forename: Yosup
authors.initials: Y
authors.lastname: Rew
authors.forename: Shelle
authors.initials: S
authors.lastname: Malkmus
authors.forename: Peter W
authors.initials: PW
authors.lastname: Schiller
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Taulane
authors.forename: Murray
authors.initials: M
authors.lastname: Goodman
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013440:Sulfides
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D013440:Sulfides; C471543:tyrosyl-(valyl-glycyl-phenylalanyl-alanyl)-OH; D020881:Enkephalin, D-Penicillamine (2,5)-; C001520:lanthionine; D000409:Alanine