μ-Opioid receptor 6-transmembrane isoform: A potential therapeutic target for new effective opioids.

Abstract

The μ-opioid receptor (MOR) is the primary target for opioid analgesics. MOR induces analgesia through the inhibition of second messenger pathways and the modulation of ion channels activity. Nevertheless, cellular excitation has also been demonstrated, and proposed to mediate reduction of therapeutic efficacy and opioid-induced hyperalgesia upon prolonged exposure to opioids. In this mini-perspective, we review the recently identified, functional MOR isoform subclass, which consists of six transmembrane helices (6 TM) and may play an important role in MOR signaling. There is evidence that 6 TM MOR signals through very different cellular pathways and may mediate excitatory cellular effects rather than the classic inhibitory effects produced by the stimulation of the major (7 TM) isoform. Therefore, the development of 6 TM and 7 TM MOR selective compounds represents a new and exciting opportunity to better understand the mechanisms of action and the pharmacodynamic properties of a new class of opioids.

• Authors: Marino Convertino, Alexander Samoshkin, Josee Gauthier, Michael S Gold, William Maixner, Nikolay V Dokholyan, Luda Diatchenko
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 62 Pg. 61-7 (Oct 01 2015) ISSN: 1878-4216 [Electronic] England
• PMID: 25485963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Analgesics, Opioid
• Protein Isoforms
• Receptors, Opioid, mu

Topics

• Analgesics, Opioid (pharmacology)
• Animals
• Humans
• Protein Conformation
• Protein Isoforms
• Receptors, Opioid, mu (genetics, metabolism)