# Development of Glycosylated Endomorphin Analogs with Low Abuse Liability for Treatment of Pain.

> **NIH VA I01** · SOUTHEAST LOUISIANA VETERANS HEALTH CARE · 2024 · —

## Abstract

Project Summary/Abstract
 Opioids acting at the mu opioid receptor (MOR) remain the gold standard for treatment of
moderate to severe pain relief, but their use is limited by serious side effects, particularly abuse
liability. The opioid epidemic has grown steadily in the past three decades, resulting in 137
deaths per day. In this program, we will test modifications of the core pharmacophore of an
endomorphin analog that has been shown to provide pain relief comparable to morphine while
exhibiting reduction of several side effects, including abuse liability. A series of glycosylated
analogs of endomorphin, designed to enhance blood-brain-barrier penetration, will be tested.
Preliminary tests indicate highly effective acute antinociception/pain relief for 2 of these
compounds. We will identify 3 candidate compounds and assess them for low abuse liability in
rodent models that correlate with human abuse liability. We will then test for reduction of
tolerance and respiratory depression relative to currently used opioids, and effective relief of 3
forms of pain ranging from moderate to chronic duration. Pharmacokinetic profiles will enable
planning of human studies. The goal of this project is to show proof-of-concept that these novel
endomorphin analogs can provide effective treatment of pain without rewarding properties and
other key adverse effects. Successful outcomes of this project will support development of these
compounds for clinical use as novel treatments for pain and potentially for opioid use disorder.

## Key facts

- **NIH application ID:** 10703798
- **Project number:** 1I01BX006167-01A1
- **Recipient organization:** SOUTHEAST LOUISIANA VETERANS HEALTH CARE
- **Principal Investigator:** James E Zadina
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10703798

## Citation

> US National Institutes of Health, RePORTER application 10703798, Development of Glycosylated Endomorphin Analogs with Low Abuse Liability for Treatment of Pain. (1I01BX006167-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10703798. Licensed CC0.

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