The long-term objective is to prepare a potent, selective inhibitor of cocaine binding at the dopamine transporter that has a minimal effect on the reuptake of dopamine. Inhibition of this binding could result in a drug useful in blunting the craving for cocaine, a substance that has severe abuse problems in a wide spectrum of the United States population. This objective will be approached by a systematic structural modification using molecular modeling techniques, of the clinically used mazindol, a known inhibitor of the cocaine binding site with a poor dopamine uptake/cocaine binding ratio (1.04). A second objective is to correlate, if possible, the structure-activity relationships (SAR) of the mazindol analogs with R-cocaine and other dopamine transporter inhibitors with the aim of designing novel inhibitors of the cocaine receptor.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA010533-02
Application #
2713146
Study Section
Human Development Research Subcommittee (NIDA)
Project Start
1997-08-15
Project End
2000-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Drew University
Department
Type
Organized Research Units
DUNS #
City
Madison
State
NJ
Country
United States
Zip Code
07940
Houlihan, William J; Kelly, Lawrence (2003) Assessment of mazindane, a pro-drug form of mazindol, in assays used to define cocaine treatment agents. Eur J Pharmacol 458:263-73
Houlihan, William J; Ahmad, Umer F; Koletar, Judith et al. (2002) Benzo- and cyclohexanomazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter. J Med Chem 45:4110-8
Houlihan, William J; Kelly, Lawrence; Pankuch, Jessica et al. (2002) Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter. J Med Chem 45:4097-109
Kulkarni, Santosh S; Newman, Amy Hauck; Houlihan, William J (2002) Three-dimensional quantitative structure-activity relationships of mazindol analogues at the dopamine transporter. J Med Chem 45:4119-27