Molecular determinants for selective recognition of antidepressants in the human serotonin and norepinephrine transporters.

ABSTRACT: Inhibitors of the serotonin transporter (SERT) and norepinephrine transporter (NET) are widely used in the treatment of major depressive disorder. Although SERT/NET selectivity is a key determinant for the therapeutic properties of these drugs, the molecular determinants defining SERT/NET selectivity are poorly understood. In this study, the structural basis for selectivity of the SERT selective inhibitor citalopram and the structurally closely related NET selective inhibitor talopram is delineated. A systematic structure-activity relationship study allowed identification of the substituents that control activity and selectivity toward SERT and NET and revealed a common pattern showing that SERT and NET have opposite preference for the stereochemical configuration of these inhibitors. Muta

SUBMITTER: Andersen J 

PROVIDER: S-EPMC3141962 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature