# AMPA Antagonism: A Novel Pharmacology for Launching Recovery from Opioid Addiction

> **NIH NIH UG3** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $1,854,492

## Abstract

PROJECT SUMMARY
The national epidemic of opioid addiction represents a public health crisis that demands new treatments.
Saving lives from overdoses and launching patients into opioid free-conditions and total illness remission,
requires transitioning through Opioid Withdrawal Syndrome (OWS). It is imperative that we find more effective
treatments for the excruciating multiday experience of OWS because this syndrome is intensified by the opioid
antagonist drugs naloxone and naltrexone, which are important to averting overdoses and facilitating long-term
recovery. NIDA has recently published its `10 Most Wanted' medication development priorities in
response to the opioid epidemic (Neuropsychopharmacology, 2019) which includes targeting of the
glutamate AMPA receptor system. This project answers this call by developing the AMPA antagonist
Tezampanel (TZP) which reduces hyperactivity in brain circuits involved in OWS, without relying on
direct stimulation or antagonism of the opioid system. TZP has been shown to reduce OWS that is
provoked by naltrexone in morphine habituated rats, and it is currently under evaluation by NIDA's Addiction
Treatment Discovery Program (ATDP) that evaluates candidates in relevant preclinical models including
cytochrome P450 assays to predict drug interactions. TZP has already been delivered to over 500 human
subjects and found to be safe for a potential migraine indication (US IND 46,811). Proniras, the
industrial partner in this application, holds an exclusive license from Eli Lilly for TZP development and
commercialization; all data generated under the migraine program (prior pharmacokinetics, clearance,
safety and efficacy in humans) will be cross referenced to a new IND for the OWS indication. The
manufacturing of clinical grade TZP for IV delivery, new rodent studies (as directed by Dr. Toombs, co-PI,
pharmacologist/Proniras), IND development meetings and submissions in year 1, will position our teams for
initial human trials of TZP for OWS in year 2 (as directed by Dr. Chambers, co-PI, addiction psychiatrist). Both
open label and blinded placebo controlled studies will be conducted in a secure, medically and psychiatrically
monitored inpatient research setting at Indiana University in Indianapolis. With the efficacy and safety data
from the UG3 phase, and guidance from NIDA and FDA, the co-PIs in the UH3 phase (years 3-5) will direct an
expansion of the research program to 3 additional U.S. academic medical centers. These sites will conduct
further testing of TZP in drug interaction studies (e.g. with opioids in non-treatment seeking subjects) and in
alternative treatment contexts (in treatment seeking subjects) to replicate and expand on the UG3 findings. In
total, the 5-year (UG3/UH3) project is expected to produce a rich safety and efficacy data set in over 250
subjects and form the basis for an end-of-phase 2 meeting with FDA. This will allow planning for a pivotal
registration trial for TZP for OWS, and as a ...

## Key facts

- **NIH application ID:** 9968676
- **Project number:** 1UG3DA050923-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** ROBERT ANDREW CHAMBERS
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,854,492
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968676

## Citation

> US National Institutes of Health, RePORTER application 9968676, AMPA Antagonism: A Novel Pharmacology for Launching Recovery from Opioid Addiction (1UG3DA050923-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968676. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*