A new medicine that targets a brain receptor to improve thinking and motivation

Muscarinic modulation of RDoC constructs in primate behavior and fronto-striatal circuits

['FUNDING_R01'] · VANDERBILT UNIVERSITY · NIH-11266141

A drug that boosts a specific brain receptor (M1) is being tested in primates to find ways to improve thinking, motivation, and control of behavior for people with conditions such as schizophrenia.

Quick facts

Phase['FUNDING_R01']
Study typeNih_funding
SexAll
SponsorVANDERBILT UNIVERSITY (nih funded)
Locations1 site (Nashville, UNITED STATES)
Trial IDNIH-11266141 on ClinicalTrials.gov

What this research studies

This project uses experiments in nonhuman primates to see whether an M1 positive allosteric modulator (M1-PAM) can improve attention, working memory, motivation, and behavioral flexibility. Researchers will compare the M1-PAM to existing cholinergic drugs (xanomeline and donepezil) and measure dose-response effects on behavior. They will also record brain electrical activity and measure neurochemical changes in frontal and striatal circuits to understand how the drug works at the cellular level. Results aim to link specific brain mechanisms to improvements in cognition and motivation that matter to patients.

Who could benefit from this research

Good fit: People with schizophrenia who have trouble with thinking, attention, motivation, or negative symptoms would be the most likely candidates for future trials of M1-PAM drugs.

Not a fit: Anyone without cognitive or motivational symptoms, or people with medical reasons to avoid cholinergic drugs, would be unlikely to benefit from this specific approach.

Why it matters

Potential benefit: If successful, this work could lead to drugs that reduce negative symptoms and cognitive problems in schizophrenia while causing fewer side effects than less-selective cholinergic medicines.

How similar studies have performed: Related cholinergic drugs like xanomeline and donepezil have shown some cognitive or symptom benefits, but selective M1-PAMs are a newer approach with limited human testing so far.

Where this research is happening

Nashville, UNITED STATES

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.

View on NIH RePORTER →

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.