Development of 3-phenyltropane analogues with high affinity for the dopamine and serotonin transporters and low affinity for the norepinephrine transporter.

ABSTRACT: Previous studies showed that the mixed monoamine transporter inhibitor (6, RTI-112) reduced cocaine self-administration at a high level of serotonin transporter (5-HTT) occupancy with no detectable dopamine transporter (DAT) occupancy. In this study, a series of 3beta-(substituted phenyl)tropane-2beta-carboxylic acid methyl esters (7a-g), 3beta-(4-methoxyphenyl)tropane-2beta-carboxylic acid esters (8a-j), and 3beta-(4-methoxyphenyl)-2beta-[3-(4'-methylphenyl)isoxazol-5-yl]tropane (9) were synthesized and evaluated for their monoamine transporter binding affinities to identify potent and selective compounds for both the DAT and 5-HTT relative to the norepinephrine transporter (NET). A number of compounds showed high binding affinities for both the DAT and 5-HTT and low affinity for the NET.

SUBMITTER: Jin C 

PROVIDER: S-EPMC2841478 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature