# Molecular Details of Psychoactive Drug Actions

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $602,028

## Abstract

PROJECT SUMMARY:
Scientific summary:
The 5-HT2-serotonin and D2-dopamine families of receptors represent essential targets for most
atypical antipsychotics as well as drugs useful in treating obesity, sleep disorders, psychosis and
autistic-spectrum disorders. It is currently unknown how these drugs interact with their target
receptors. Here we aim to obtain high resolution structures of 5-HT2A- and 5-HT2B- serotonin and D2-
and D4-dopamine receptors with an array of small molecules. These studies are both innovative
technically and conceptually by providing an unprecedented understanding of the molecular and
atomic details responsible for psychoactive drug actions. Technical achievements will include
the structure of LSD in complex with its key serotonin receptor targets and typical and
atypical antipsychotic drugs in complex with their serotonin and dopamine receptor targets.
Additionally, models which attempt to explain ligand-specific properties of biased signaling from the
perspective of ligand-receptor interactions will be tested by a combination of direct structural studies,
molecular modeling, docking, site-directed mutagenesis and functional studies. We anticipate that
our studies will reveal key ligand-receptor interactions essential for biased signaling for serotonin and
dopamine receptors. Elucidating the molecular details for such interactions provides a
template for the structure-guided design of novel therapeutics.

## Key facts

- **NIH application ID:** 9839677
- **Project number:** 5R01MH112205-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Bryan L. Roth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $602,028
- **Award type:** 5
- **Project period:** 2017-03-06 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9839677

## Citation

> US National Institutes of Health, RePORTER application 9839677, Molecular Details of Psychoactive Drug Actions (5R01MH112205-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9839677. Licensed CC0.

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