title: Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands.
abstract: Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, 2036 Health Sciences North, Morgantown, WV 26506, USA; Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1170 Main Bldg., 132 S. 10th St., Philadelphia, PA 19107, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Healy
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA.
authors.forename: Padmavani
authors.initials: P
authors.lastname: Bezawada
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, 1220A MSRB, Ann Arbor, MI 48109, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Griggs
authors.affiliation: Department of Pharmaceutical Sciences, Concordia University Wisconsin School of Pharmacy, 12800 N. Lake Shore Drive, Mequon, WI 53097, USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Devereaux
authors.affiliation: Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, 2036 Health Sciences North, Morgantown, WV 26506, USA; Department of Biological and Pharmaceutical Sciences, Touro University California College of Pharmacy, 1310 Club Drive, Vallejo, CA 94592, USA.
authors.forename: Rae R
authors.initials: RR
authors.lastname: Matsumoto
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, 1220A MSRB, Ann Arbor, MI 48109, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Coop
authors.affiliation: Department of Pharmaceutical Sciences, Concordia University Wisconsin School of Pharmacy, 12800 N. Lake Shore Drive, Mequon, WI 53097, USA. Electronic address: chris.cunningham@cuw.edu.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Cunningham
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000818:Animals; D001597:Benzylidene Compounds / Q000737:chemistry; D008024:Ligands; D051379:Mice; D010111:Oxymorphone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*
chemical_list: C000621043:7-benzylideneoxymorphone; D000700:Analgesics; D001597:Benzylidene Compounds; D008024:Ligands; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D010111:Oxymorphone
keywords: Analgesic tolerance; Benzylideneoxymorphone; Delta opioid receptor; Mu opioid receptor; Oxymorphone