• Skip to primary navigation
  • Skip to main content
SRI logo
  • About
    • Press room
    • Our history
  • Expertise
    • Advanced imaging systems
    • Artificial intelligence
    • Biomedical R&D services
    • Biomedical sciences
    • Computer vision
    • Cyber & formal methods
    • Education and learning
    • Innovation strategy and policy
    • National security
    • Ocean & space
    • Quantum
    • Robotics, sensors & devices
    • Speech & natural language
    • Video test & measurement
  • Ventures
  • NSIC
  • Careers
  • Contact
  • 日本支社
Search
Close
Biomedical sciences publications September 1, 2009

Comparison of the Antinociceptive and Antirewarding Profiles of Novel Bifunctional Nociceptin Receptor/Mu-Opioid Receptor Ligands: Implications for Therapeutic Applications

Citation

Copy to clipboard


Lawrence Toll, Taline V. Khroyan, Willma E. Polgar, Faming Jiang, Cris Olsen and Nurulain T. Zaveri Journal of Pharmacology and Experimental Therapeutics December 2009, 331 (3) 954-964; DOI: https://doi.org/10.1124/jpet.109.157446

Abstract

The nociceptin receptor (NOPr), a member of the opioid receptor family, is a target for the treatment of pain and drug abuse. Nociceptin/orphanin FQ (N/OFQ), the endogenous peptide for NOPr, not only modulates opioid antinociception, but also blocks the rewarding effects of several abused drugs, such as morphine, cocaine, and amphetamine. We hypothesized that NOPr agonists, with bifunctional activity at the μ-opioid receptor (MOPr), may function as nonaddicting analgesics or as drug abuse medications. Bifunctional small-molecule NOPr agonists possessing different selectivities and efficacies at MOPr were evaluated in an acute thermal antinociception assay, and for their ability to induce conditioned place preference (CPP) and their effect on morphine-induced CPP. 1-(1-Cyclooctylpiperidin-4-yl)-indolin-2-one) (SR14150), a high-affinity NOPr partial agonist, with low MOPr affinity and efficacy, produced analgesia that was naloxone-reversible. SR14150 did not induce CPP alone, nor did it attenuate morphine-induced CPP. 3-Ethyl-1-(1-(4-isopropylcyclohexyl)piperidin-4-yl)-indolin-2-one (SR16507), which has high affinity for both NOPr and MOPr, full agonist activity at NOPr, and partial agonist activity at MOPr, was also a potent analgesic and produced CPP alone, but also modestly attenuated morphine CPP. 1-(1-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)piperidinl-4-yl)-indolin-2-one (SR16835), a NOPr full agonist and low-affinity MOPr partial agonist, was not antinociceptive, did not produce CPP alone, but attenuated morphine CPP. Our results suggest that NOPr full-agonist activity is required to modulate opioid-induced reward, whereas a bifunctional NOPr/MOPr partial agonist profile may be suitable as a nonaddicting analgesic. The opioid-modulating effects of the NOPr ligands may be used effectively to produce better medications for treatment of drug abuse and pain.

↓ View online

Share this
Career call to action image

Work with us

Search jobs

How can we help?

Once you hit send…

We’ll match your inquiry to the person who can best help you.

Expect a response within 48 hours.

Our work

Case studies

Publications

Timeline of innovation

Areas of expertise

Institute

Leadership

Press room

Media inquiries

Compliance

Careers

Job listings

Contact

SRI Ventures

Our locations

Headquarters

333 Ravenswood Ave
Menlo Park, CA 94025 USA

+1 (650) 859-2000

Subscribe to our newsletter


日本支社
SRI International
  • Contact us
  • Privacy Policy
  • Cookies
  • DMCA
  • Copyright © 2023 SRI International
Manage Cookie Consent
To provide the best experiences, we use technologies like cookies to store and/or access device information. Consenting to these technologies will allow us to process data such as browsing behavior or unique IDs on this site. Not consenting or withdrawing consent, may adversely affect certain features and functions.
Functional Always active
The technical storage or access is strictly necessary for the legitimate purpose of enabling the use of a specific service explicitly requested by the subscriber or user, or for the sole purpose of carrying out the transmission of a communication over an electronic communications network.
Preferences
The technical storage or access is necessary for the legitimate purpose of storing preferences that are not requested by the subscriber or user.
Statistics
The technical storage or access that is used exclusively for statistical purposes. The technical storage or access that is used exclusively for anonymous statistical purposes. Without a subpoena, voluntary compliance on the part of your Internet Service Provider, or additional records from a third party, information stored or retrieved for this purpose alone cannot usually be used to identify you.
Marketing
The technical storage or access is required to create user profiles to send advertising, or to track the user on a website or across several websites for similar marketing purposes.
Manage options Manage services Manage {vendor_count} vendors Read more about these purposes
View preferences
{title} {title} {title}