# Development of IM Formulation of (2S,3S)-SPD for Nerve Agent Seizures

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $712,030

## Abstract

Project Summary/Abstract
 This project seeks to advance the development of (2S,3S)-sec-butylpropylacetamide [(2S,3S)-SPD] for the
treatment of chemical threat agent seizures. A priority of the NIH CounterACT Program is the development of
medical countermeasures to treat seizures induced by anticholinesterase nerve agents such as soman and
sarin or GABA-inhibiting agents such as tetramethylenedisulfotetramine (TETS). Benzodiazepines, the current
standard-of-care therapies, fail to stop seizures induced by such agents when there is more than a brief delay
between onset of seizures and administration of the treatment agent. In rodents, (2S,3S)-SPD is a broad-
spectrum antiseizure agent that effectively stops benzodiazepine-resistant behavioral and electrographic status
epilepticus in the lithium-pilocarpine model. Moreover, studies conducted at the U.S. Army Medical Research
Institute of Chemical Defense indicate that (2S,3S)-SPD rapidly stops soman-induced benzodiazepine-
resistant SE in rats at delayed time points, an effect not shared by benzodiazepines or other antiseizure drugs.
Therefore, (2S,3S)-SPD has promise to provide a major improvement to the current standard-of-care for the
treatment of nerve agent seizures. The objective of the proposed research is to generate the data required to
advance the development of an intramuscular formulation (2S,3S)-SPD so that it is available as a medical
countermeasure for nerve agent seizures in the setting of a civilian exposure. A scalable synthesis route for
(2S,3S)-SPD will be developed. The API will be formulated in a solution designed for intramuscular
administration, a “mass-casualty-friendly” route of delivery that offers fast onset of action. Initial toxicology and
safety studies will be conducted in animals, including studies to assess safety in both males and females and
in special populations such as children. Additional proof-of-concept and dose-ranging studies in relevant
animal models will be conducted, including in a model of TETS-induced status epilepticus. The proposed
research will assess the potential of (2S,3S)-SPD as an improved medical countermeasure to treat seizures
induced by diverse chemical threat agents. On completion of the project, a comprehensive set of data will be
available to advance the development of (2S,3S)-SPD as an improved treatment for chemical threat agent
seizures.

## Key facts

- **NIH application ID:** 9991952
- **Project number:** 5U01NS112102-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Meir Bialer
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $712,030
- **Award type:** 5
- **Project period:** 2019-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991952

## Citation

> US National Institutes of Health, RePORTER application 9991952, Development of IM Formulation of (2S,3S)-SPD for Nerve Agent Seizures (5U01NS112102-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991952. Licensed CC0.

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