Azidobupramine: A novel chemical tool to enlighten antidepressants’ mode of action

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

Svenja Reinders

Max-Planck-Institute for Psychiatry, Germany

Posters-Accepted Abstracts: Med chem

Abstract :

Antidepressants were discovered in the 1950s but their underlying molecular mechanisms are still incompletely understood. Revealing the identity of additional targets may contribute to a better understanding of the antidepressants� mode of action. The aim of this study was to develop a chemically modified antidepressant enabling the identification of alternative direct drug targets. For this purpose, azidobupramine, a structurally related analogue of imipramine, was synthesized featuring two additional chemical groups, one for Photo-Affinity Labeling (PAL) and the other for Copper (I) Catalyzed Azide Alkyne Cycloaddition (CuAAC). Using the serotonin transporter as model target, we demonstrate that azidobupramine is characterized by equilibrium dissociation constants (Ki) equivalent to those of clinically active substances. Furthermore, we show that azidobupramine forms chemical bonds with the transporter after UV light exposure in living cells. Thus, azidobupramine represents a promising and versatile tool for the discovery of novel direct antidepressant target sites in living systems.

Biography :

Email: svenja_reinders@psych.mpg.de