# Methocinnamox (MCAM): A novel õ-opioid receptor antagonist for opioid use disorders

> **NIH NIH UG3** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $147,995

## Abstract

ABSTRACT/SUMMARY
This application for a supplement to parent grant UG3DA048387 is in response to Notice of Special Interest
NOT-DA-21-032 “Administrative Supplements for research on fentanyl and derivatives.” The opioid crisis
has worsened significantly during the COVID-19 pandemic, in part because of increasing availability of fentanyl
and potent fentanyl analogs. Many overdoses involve more than one drug, often an opioid and a stimulant drug,
although it is unclear whether stimulants alter the toxic effects of opioids and reversal of those effects by
naloxone. The value of naloxone is limited by its short duration of action and that its antagonism can be
surmounted by taking more agonist. After rescue from overdose, protection by naloxone often wanes before the
effects of the opioid receptor agonist decrease, resulting in the reemergence of ventilatory depression possibly
leading to death. Fatal ventilatory depression can occur in the presence of naloxone if an individual continues
taking opioids, and there are reports of the need for larger doses and/or more frequent administration of
naloxone to reverse and protect against overdose from fentanyl, compared with reversal of overdose from other
opioids. Methocinnamox (MCAM) is a long-acting µ opioid receptor antagonist that reverses and prevents the
ventilatory-depressant effects of fentanyl. It is not known whether MCAM is equally effective (potent) in
reversing ventilatory depression by different opioids. Some studies suggest that opioid receptor antagonists, such
as naloxone and naltrexone, do not block effects of different opioids equally and that mixtures of antagonists
might be more effective than antagonists alone. Studies in this proposal will address the following: 1) investigate
reversal of and protection from ventilatory depression by heroin and by fentanyl and related analogs; 2) compare
the novel opioid receptor antagonist MCAM with naloxone and MCAM/naloxone mixtures; 3) characterize the
ventilatory-depressant effects of heroin/methamphetamine and fentanyl/methamphetamine mixtures and
reversal of those effects by naloxone and MCAM, alone and together; and 4) test for sex differences in the
ventilatory-depressant effects of opioids and reversal of those effects by naloxone and MCAM, alone and
together. Two specific aims will test the following hypotheses: 1) naloxone is less potent at reversing ventilatory
depression by fentanyl and related analogs compared with reversal of ventilatory depression by heroin; 2)
MCAM has similar potency at reversing ventilatory depression by all four opioids; 3) methamphetamine does
not alter the ventilatory-depressant effects of fentanyl or heroin nor reversal of those effects by antagonists;
4) mixtures of MCAM and naloxone are more effective than either antagonist alone at reversing and protecting
against ventilatory depression; and 5) there are no sex differences in the effects of drugs in this study. By
characterizing reversal of ventilatory depr...

## Key facts

- **NIH application ID:** 10477526
- **Project number:** 3UG3DA048387-01A1S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** CHARLES P FRANCE
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $147,995
- **Award type:** 3
- **Project period:** 2019-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477526

## Citation

> US National Institutes of Health, RePORTER application 10477526, Methocinnamox (MCAM): A novel õ-opioid receptor antagonist for opioid use disorders (3UG3DA048387-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10477526. Licensed CC0.

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