# Evaluation of the therapeutic potential of exclusive antagonists of extrasynaptic NMDA receptors for the treatment of opioid use disorder

> **NIH NIH R44** · NEURANO BIOSCIENCE · 2024 · $837,882

## Abstract

PROJECT SUMMARY
 Opioid use in the United States has been at epidemic proportions for many years. Concerted efforts across
the spectrum of political, social awareness, clinical and research initiatives have so far been unable to curb the
rising rates of opioid use and opioid overdose deaths across the USA. From the treatment standpoint, a number
of novel therapies to alleviate the severe opioid withdrawal symptoms and/or reduce risk of relapse continue to
be proposed. A significant portion of research into potential therapies focuses on testing FDA-approved drugs
as potential treatments for opioid use. Such approach relies on the verified scientific rationale and clinically
validated drug targets to ensure that these studies will produce efficacious new drugs for opioid use disorder.
 One of such drugs is memantine, an NMDA receptor antagonist, that has shown encouraging results as an
adjunct to existing opioid use therapies. Therapeutics effects of memantine are due to the involvement of
glutamatergic pathways in the development and maintenance of opioid addiction, and its clinical tolerability likely
derives from preferential inhibition of NMDA receptors located outside the synapse, since broad spectrum NMDA
receptor antagonists are associated with serious clinical side effects. However, memantine concentrations must
be kept low to take advantage of its preferential antagonism, because at higher (and more therapeutically
relevant) concentrations, memantine may inhibit synaptic NMDA receptors and trigger side effects.
 To resolve this problem, NeurANO Bioscience created a nanoparticle-based (AuM) conjugate comprising
several memantine molecules. Due to its dimensions, AuM cannot access the synaptic cleft and synaptic NMDA
receptors, but allows activation of extrasynaptic NMDAR receptors with the potency greatly exceeding that of
free memantine. During Phase I studies, we discovered that AuM can drastically minimize the opioid withdrawal
symptoms, and demonstrated that AuM can be delivered into the brain at therapeutic concentrations using
intranasal administration. During proposed Phase II studies, we will proceed with efforts directed at establishing
the commercial manufacturability of AuM, determining optimal administration routes and AuM dosage for the
treatment of opioid withdrawal symptoms, and exploring AuM therapeutic potential for the prevention of
acquisition of opioid dependence and/or relapse. Using the data acquired during Phase II studies, we will
develop the efficient strategy to pursue IND-enabling studies for use of exclusive antagonists of extrasynaptic
NMDARs in the treatment of OUD.

## Key facts

- **NIH application ID:** 10837882
- **Project number:** 5R44DA050393-03
- **Recipient organization:** NEURANO BIOSCIENCE
- **Principal Investigator:** ELENA MOLOKANOVA
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $837,882
- **Award type:** 5
- **Project period:** 2019-09-30 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837882

## Citation

> US National Institutes of Health, RePORTER application 10837882, Evaluation of the therapeutic potential of exclusive antagonists of extrasynaptic NMDA receptors for the treatment of opioid use disorder (5R44DA050393-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10837882. Licensed CC0.

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