A novel approach to treating opioid use disorders: Dual agonists of glucagon-like peptide-1 receptors and neuropeptide Y2 receptors

Riley Merkel, Amanda Moreno, Yafang Zhang, Rachel Herman, Jennifer Ben Nathan, Sana Zeb, Suditi Rahematpura, Kamryn Stecyk, Brandon T. Milliken, Matthew R. Hayes, Robert P. Doyle, Heath D. Schmidt

Research output: Contribution to journalReview articlepeer-review

Abstract

The widespread misuse of opioids and opioid use disorder (OUD) together constitute a major public health crisis in the United States. The greatest challenge for successfully treating OUD is preventing relapse. Unfortunately, there are few FDA-approved medications to treat OUD and, while effective, these pharmacotherapies are limited by high relapse rates. Thus, there is a critical need for conceptually new approaches to developing novel medications to treat OUD. Here, we review an emerging preclinical literature that suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists could be re-purposed for treating OUD. Potential limitations of this approach are also discussed along with an alternative strategy that involves simultaneously targeting and activating GLP-1Rs and neuropeptide Y2 receptors (Y2Rs) in the brain using a novel monomeric dual agonist peptide. Recent studies indicate that this combinatorial pharmacotherapy approach attenuates voluntary fentanyl taking and seeking in rats without producing adverse effects associated with GLP-1R agonist monotherapy alone. While future studies are required to comprehensively determine the behavioral effects of GLP-1R agonists and dual agonists of GLP-1Rs and Y2Rs in rodent models of OUD, these provocative preclinical findings highlight a potential new GLP-1R-based approach to preventing relapse in humans with OUD.

Original languageEnglish (US)
Pages (from-to)1169-1179
Number of pages11
JournalNeuroscience and Biobehavioral Reviews
Volume131
DOIs
StatePublished - Dec 2021

Keywords

  • Drug self-administration
  • Exendin-4
  • GLP-1
  • Opioid
  • PYY
  • Reinstatement
  • Relapse

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Fingerprint

Dive into the research topics of 'A novel approach to treating opioid use disorders: Dual agonists of glucagon-like peptide-1 receptors and neuropeptide Y<sub>2</sub> receptors'. Together they form a unique fingerprint.

Cite this