NOVEL BENZTROPINE [3-ALPHA-(DIPHENYLMETHOXY)TROPANE] ANALOGS AS PROBES FOR THE DOPAMINE TRANSPORTER

The design, synthesis and pharmacological evaluation of novel dopamine transporter ligands, based on Benztropine [3 alpha-(diphenylmethoxy) tropane], has been a focus of our research efforts toward the developm ent of novel cocaine-abuse pharmacotherapeutics. Structure-activity re lationships at the dopamine transporter, for this series of compounds, have been derived and compared to those of cocaine and GBR 12909. The se studies suggest that structurally diverse dopamine uptake inhibitor s may access different binding domains on the dopamine transporter. Th e distinctive behavioral profile displayed in this series of compounds , as compared to cocaine and other dopamine uptake inhibitors, is of p articular interest and is proposed to be relevant to the pharmacodynam ic and pharmacokinetic properties of this class of tropane-based molec ules.