# STRUCTURAL DOMAINS AND SEROTONIN RECEPTOR PHARMACOLOGY

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1994 · $179,733

## Abstract

Alterations in the functional activity and/or number of serotonin2 (5-HT2)
and/or serotonin1C (5-HT-1c) receptors have been implicated in the
pathophysiology of a large number of mental illnesses including obsessive-
compulsive disorder, schizophrenia, depression, anxiety, dysthymia,
suicide, aggression and eating disorders. Additionally, a number of
psycho- and neuropharmacologic agents including antidepressants
(mianserin, amitriptyline, imipramine), antipsychotic drugs (loxapine,
clozapine), hallucinogens (lysergic acid diethylamide) and anti-dysthymic
agents (ritanserin) bind to 5-HT2 and 5-HT-1c receptors. Determining the
precise roles the 5-HT2 and 5-HT-1c receptors have in mediating the
effects of these agents is difficult because no truly subtype selective
agents are currently available. Insights we gain in understanding how
drugs bind to each of these receptors should enhance our ability to design
novel receptor-specific agents which can be used to treat mental
illnesses.

This proposal will determine how agonists and antagonists bind to 5-HT2
and 5-HT-1c receptors. We will utilize the techniques of molecular biology
and receptor pharmacology to identify specific amino acids essential for
specifying the ligand binding domains of each receptor. We are utilizing
four major techniques.  (1) chimeric protein construction (2) site
directed mutagenesis, (3) molecular modelling and (4) structural
biochemical measurements. Our strategy is to test three-dimensional
molecular models of 5- HT2 and 5- HT-1c receptor-ligand interactions using
a combination of molecular biological and structural-biochemical
techniques. We will also take advantage of unique mutations we have
produced to probe the molecular details responsible for hallucinogen-
induced alterations of serotonin receptors in vitro. These findings will
be useful for the design and synthesis of new medications to treat
psychiatric diseases.

## Key facts

- **NIH application ID:** 2191152
- **Project number:** 1R01GM052213-01
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** Bryan L. Roth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $179,733
- **Award type:** 1
- **Project period:** 1994-07-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2191152

## Citation

> US National Institutes of Health, RePORTER application 2191152, STRUCTURAL DOMAINS AND SEROTONIN RECEPTOR PHARMACOLOGY (1R01GM052213-01). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/2191152. Licensed CC0.

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