# Development of compound RUEC2-118, a novel partial GABAAR positive modulator, a fast-acting treatment for general anxiety and panic disorder, to prevent opioid and benzodiazepine overdose fatalities.

> **NIH NIH R41** · ZENA THERAPEUTICS INC. · 2024 · $55,000

## Abstract

Co-occurring anxiety is prevalent in more than 50% of individuals with Opioid use disorder (OUD). This is of
major concern as safe and effective treatment options are lacking for this high-risk population. Anxiety in those
with OUD is linked to earlier and more rapid progression of OUD, and high probability of co-use of other
substances, particularly GABAA receptor positive modulators, such as benzodiazepines (BZDs). BZDs are
currently the standard of care treatment for fast-acting relief for general anxiety and panic disorder. Although
highly effective in the short-term, BZDs represent amajor, but often overlookedcontributorto the opioid overdose
epidemic. BZDs are involved in an estimated 12,000 overdose fatalities each year in the US, largely due to the
concomitant use with other CNS depressants, such as opioids. In fact, more than 90%of BZD overdose fatalities
involve opioids and up to 30% opioid overdoses involve BZDs. Additionally, BZD prescription rates are directly
linked to opioid overdose rates per state. With a lack of safe alternatives that can offer comparable efficacy, BZD
market predictions indicate their use will remain steady or increase globally. Thus, there is an urgent need to
develop safe and comparably effective alternatives to BZDs for those with OUD. We have discovered a novel
series of promising synthetic GABAAR active molecules Our lead molecule, RU-EC2-118, is a partial GABAAR
PAM with nanomolar potency at GABAAR subtypes and high oral bioavailability. Our in vivo studies in rodent
models, strongly support the potential for the mechanismof RUEC2-118 to provide effective fast-actinganxiolytic
activity and a safer profile with co-use with other CNS-depressing substances. The major technical aims of the
STTR parent grant is to provide proof-of-concept data supporting the feasibility of our approach in maintaining
efficacy and reducing overdoserisks. Specific aim3 is to test the desirability of our innovation through enrollment
in the NIH I-Corps program. Having previously completed the NSF National ICorps program, we successfully
validated the need for our innovation. During the NIH ICorps program, our main objective is to further investigate
the best pathways towards funding and commercialization of our innovation .

## Key facts

- **NIH application ID:** 10987840
- **Project number:** 3R41DA058472-01S1
- **Recipient organization:** ZENA THERAPEUTICS INC.
- **Principal Investigator:** Eileen Carry
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $55,000
- **Award type:** 3
- **Project period:** 2024-02-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987840

## Citation

> US National Institutes of Health, RePORTER application 10987840, Development of compound RUEC2-118, a novel partial GABAAR positive modulator, a fast-acting treatment for general anxiety and panic disorder, to prevent opioid and benzodiazepine overdose fatalities. (3R41DA058472-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10987840. Licensed CC0.

---

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