Format

Send to

Choose Destination
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Oct 1;62:61-7. doi: 10.1016/j.pnpbp.2014.11.009. Epub 2014 Dec 6.

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

Author information

1
Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC 27599, USA.
2
The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec H3A 0G1, Canada.
3
Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC 27599, USA.
4
Department of Anesthesiology, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15213, USA.
5
Center for Pain Research and Innovation, University of North Carolina, 385 S. Columbia St., CB #7455, KOHSB, Chapel Hill, NC 27599, USA. Electronic address: bill_maixner@dentistry.unc.edu.
6
Biochemistry and Biophysics Department, University of North Carolina, 120 Mason Farm Rd., CB #7260 Genetic Medicine, Chapel Hill, NC 27599, USA. Electronic address: dokh@unc.edu.
7
The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec H3A 0G1, Canada. Electronic address: luda.diatchenko@mcgill.ca.

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.

KEYWORDS:

6TM MOR isoform; Drug discovery; Review; μ-Opioid receptor

PMID:
25485963
PMCID:
PMC4646084
DOI:
10.1016/j.pnpbp.2014.11.009
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center