Effects of two-carbon bridge region methoxylation of benztropine: Discovery of novel chiral ligands for the dopamine transporter

6-Methoxylated and 8-oxygenated benztropines were prepared and evaluated fo r their DAT and SERT activity (binding and uptake inhibition). Methoxylatio n at the two-carbon bridge of benztropine produced a novel class of potent and selective DAT ligands. An interesting enantioselectivity was also obser ved for this new class of chiral benztropines. The inactivity of the 8-oxyg enated analogues seems to point out that, unlike cocaine and its analogues, interactions of benztropine ligands with DAT may be strongly governed by t he nitrogen atom. (C) 2001 Elsevier Science Ltd. All rights reserved.