The goal of this project is to develop a novel agonist radioligand for evaluating the proportion of D2 receptors in the high state. The D2high receptor is thought to be the functional form of the D2 receptor to which endogenous dopamine binds. An agonist radioligand should be more sensitive to endogenous DA levels than antagonist radioligands since, unlike antagonists, agonist radioligands bind preferentially to the receptor in its high affinity state. Thus, agonist radioligands have the potential to elucidate more detailed information on receptor subtype activity as a function of disease as well as DA system activity as a whole. The majority of available radioligands are based on D2 antagonists and, as such, do not specifically target the D2high state. Among the commercially available agonist ligands, none possess high selectivity for D2 over D3. In contrast, fluoroaporphines, which are the focus of this project, are D2 receptor agonists that specifically and selectively target D2high receptors. The objective of this project is, therefore, to develop 3H-labeled fluoroaporphines as radioligands for in vitro binding studies and for autoradiography to aid in the evaluation and study of the role of the D2high receptor function in the brain.

Public Health Relevance

The goal of this project is to develop a novel agonist radioligand for evaluating the proportion of D2 receptors in the high state, which is thought to be the functional form of the D2 receptor to which endogenous dopamine binds. The majority of available radioligands are based on D2 antagonists and, as such, do not specifically target the D2high state;among the commercially available agonist ligands, none possess high selectivity for D2 over D3. The objective of this project is, therefore, to develop 3H-labeled fluoroaporphines as radioligands with high affinity and high selectivity for the D2 receptor, for i vitro binding studies and for autoradiography to aid in the evaluation and study of the role of the D2high receptor function in the brain.

Agency
National Institute of Health (NIH)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43OD020186-01A1
Application #
8775067
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Contreras, Miguel A
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Natural Pharmacia International, Inc.
Department
Type
DUNS #
City
Burlington
State
MA
Country
United States
Zip Code
01803