# Dopamine and Sigma Receptor Mixed Modulators for the Treatment of Alzheimer's Disease

> **NIH NIH R16** · SOUTHERN ILLINOIS UNIV AT EDWARDSVILLE · 2024 · $141,647

## Abstract

An estimated 1-in-8 individuals over the age of 65 has Alzheimer’s disease (AD), with a prevalence
of 1-in-3 for those over age 85. There are approximately 5.8 million people in the USA with AD, with
a global projection of over 150 million by 2050. Given the limited state of therapeutic options, a
viable therapeutic approach that is not redundant with current medications would be of great benefit
to AD patients and caregivers. Sigma receptors (σ1 and σ2) and dopamine receptors (D2 and D3)
have been respectively attracting attention as brain targets for Alzheimer’s disease (AD) treatment.
We have developed a small molecule (AM73) with affinity for σ1/σ2 and D2/D3 receptors. This mixed
modulator approach is novel and presents a viable means to treat cognitive decline and associated
symptomology. This proof-of-concept study evaluates the mixed modulator AM73 in a mouse model
of cognitive decline and AD. Aims of the study focus on determining the effect of chronic treatment of
AM73 across a dose-response respective to behavior and locomotor responses in male and female
mice. Key brain regions associated with AD pathology and targeted receptors will be evaluated for
changes in mRNA and protein expression respective to pathological indicators and treatment
markers. The goal and aims of this study address priorities of National Institute on Aging.

## Key facts

- **NIH application ID:** 10844050
- **Project number:** 1R16NS140308-01A1
- **Recipient organization:** SOUTHERN ILLINOIS UNIV AT EDWARDSVILLE
- **Principal Investigator:** KEN A WITT
- **Activity code:** R16 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $141,647
- **Award type:** 1
- **Project period:** 2024-06-04 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844050

## Citation

> US National Institutes of Health, RePORTER application 10844050, Dopamine and Sigma Receptor Mixed Modulators for the Treatment of Alzheimer's Disease (1R16NS140308-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10844050. Licensed CC0.

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