Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
ACS Chem Biol. 2011 Dec 16;6(12):1375-81. doi: 10.1021/cb200263q. Epub 2011 Oct 11.

Development and in vitro characterization of a novel bifunctional μ-agonist/δ-antagonist opioid tetrapeptide.

Author information

  • 1Medical School and College of Pharmacy, Department of Pharmacology, University of Michigan, Ann Arbor 48109, USA.

Abstract

The development of tolerance to and dependence on opioid analgesics greatly reduces their long-term usefulness. Previous studies have demonstrated that co-administration of a μ-opioid receptor (MOR) agonist and δ-opioid receptor (DOR) antagonist can decrease MOR agonist-induced tolerance and dependence development after chronic exposure. Clinically, a single ligand displaying multiple efficacies (e.g., MOR agonism concurrently with DOR antagonism) would be of increased value over two drugs administered simultaneously. Guided by modeling of receptor-ligand complexes we have developed a series of potent non-selective opioid tetrapeptides that have differing efficacy at MOR and DOR. In particular, our lead peptide (KSK-103) binds with equal affinity to MOR and DOR but acts as a MOR agonist with similar efficacy but greater potency than morphine and a DOR antagonist in cellular assays measuring both G protein stimulation and adenylyl cyclase inhibition.

PMID:
21958158
[PubMed - indexed for MEDLINE]
PMCID:
PMC3241856
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Write to the Help Desk