This project proposes to systematically study the conformational structure of various analogues of serotonin (5-hydroxytryptamine, 5-HT) in relation to their possible agonist and/or antagonist properties at 5-HT receptors. To this end a variety of rigid analogues patterned after the known tetrahydropyridylindoles, RU28253 and RU24969, and/or 5-HT will be synthesized and evaluated for activity in ligand-binding assays for 5-HT receptors and in tests for functional 5-HT receptors. Ligand binding tests will include those for tryptaminergic (putative), alpha1-adrenergic and dopaminergic receptors as well as those for 5-HT-1 and 5-HT-2 receptors. Tests for functional 5-HT receptor activity will include the use of various vascular preparations (e.g., canine basilar artery and rat femoral artery), behavioral tests (e.g., 5-HT behavioral syndrome and head twitch in rats), and biochemical experiments (5-HT sensitive adenylate cyclase). The goal of the project will be to determine the conformation(s) required for the actions of 5-HT at various types of 5-HT receptors. It is also possible that new 5-HT receptor antagonists will be discovered and that both 5-HT agonists and antagonists with greater selectivity will result from this study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021715-02
Application #
3403172
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1985-09-09
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Arizona
Department
Type
Schools of Pharmacy
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85722