The purpose of this contract is to determine the in vitro affinity for and inhibitory activity of test compounds on the human dopamine, serotonin and norepinephrine transporters. The data generated by this contract will be utilized by the NIDA Medications Development Division Cocaine Treatment Discovery Program in the selection of compounds for in vivo preclinical evaluations. Cocaine and a number of other abused substances bind to each of the biogenic amine transporters, and block the uptake of the respective neurotransmitter. This effect is hypothesized to play a crucial role in cocaine's reinforcing effects and potential for addition, and represents a logical target for medication development efforts. Further, recent work on NIDA Contract N01DA38303 indicates that, using novel compounds, it is possible to separate the affinity of a drug for the cocaine binding site on the transporter from its potency at blocking neurotransmitter uptake. Thus, this contract will seek to identify drugs that have a high affinity for the cocaine binding site, and prevent the binding of cocaine, but have a relatively low potency at blocking neurotransmitter uptake.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research and Development Contracts (N01)
Project #
N01DA078071-001
Application #
2662859
Study Section
Project Start
1997-05-01
Project End
2000-04-30
Budget Start
1997-09-29
Budget End
1998-04-30
Support Year
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Eshleman, A J; Wolfrum, K; Mash, D C et al. (2001) Drug interactions with the dopamine transporter in cryopreserved human caudate. J Pharmacol Exp Ther 296:442-9
Janowsky, A; Mah, C; Johnson, R A et al. (2001) Mapping genes that regulate density of dopamine transporters and correlated behaviors in recombinant inbred mice. J Pharmacol Exp Ther 298:634-43
Eshleman, A J; Carmolli, M; Cumbay, M et al. (1999) Characteristics of drug interactions with recombinant biogenic amine transporters expressed in the same cell type. J Pharmacol Exp Ther 289:877-85