The overall goal of this small grant application is the design of new dopamine receptor ligands that could be used in the management of schizophrenia and to further characterize the relationship between this syndrome and dopamine receptor subtypes. To accomplish this goal, we will use the techniques of computational chemistry to identify and characterize molecular modulators of receptor recognition and activation at the dopamine receptor subtypes. We will first determine structural and electronic properties that modulate recognition at the Dl and D2 receptor subtypes. The comparative study of the molecular modulators of recognition for both receptor subtypes will allow the determination of a set of properties that could be used in the design of more selective compounds at each receptor subtypes. Thus, the properties found to increase or decrease affinity for one receptor without significantly affecting affinity at the other could be used to selectively increase affinity at either receptor subtypes. Second, we will determine stereoelectronic properties that modulate activation for D1 and for D2 receptor subtypes. The stereoelectronic modulators determined can then be used in the design of new highly selective compounds with varied affinities and efficacies for both receptors, which can then be used in the characterization of the relationship between dopamine receptor subtypes and antipsychotic properties.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Small Research Grants (R03)
Project #
5R03DA007100-02
Application #
2119397
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1991-06-01
Project End
1993-11-30
Budget Start
1992-06-01
Budget End
1993-11-30
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Molecular Research Institute
Department
Type
DUNS #
017430633
City
Palo Alto
State
CA
Country
United States
Zip Code
94303