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.
| 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 |
