Interactions of antidepressants with the serotonin transporter: a contemporary molecular analysis

One of the most prevalent disorders in present society is depression. The development of treatments for this disorder, beginning with the tricyclic antidepressants and leading to the development of selective serotonin reuptake inhibitors, has focused on compounds that block the function of the serotonin transporter (SERT). In this paper, we have performed Comparative Molecular Field Analysis (CoMFA) using data generated from rat brain synaptosomes and heterologous expression systems expressing rat SERT. Using these models, we have described the molecular requirements for the interactions of antidepressants with SERTs. In addition, molecular studies were performed using chimeric human/Drosophila SERTs and SERT point mutants. These studies focused on identifying regions or discrete amino acids on SERT that may be responsible for recognizing antidepressants. (C) 2003 Elsevier B.V. All rights reserved.