The AAPS Journal

, Volume 7, Issue 2, pp E421–E433 | Cite as

Serotonin transporters: Implications for antidepressant drug development

  • Kellie J. White
  • Crystal C. Walline
  • Eric L. Barker


Due to the complexity of the disease, several hypotheses exist to explain the etiology of depression. The monoamine theory of depression suggests that disruptions in the serotonergic and noradrenergic systems result in depressive symptoms. Therefore, the serotonin transporter (SERT) has become a pharmacological target for treating these symptoms. This review will discuss what is known about the molecular interactions of antidepressants with SERT. The effects of antidepressants on SERT regulation and expression in addition to the receptors that may be involved in mediating these effects will be addressed. Specifically, how changes to SERT expression following chronic antidepressant treatment may contribute to the therapeutic benefits of antidepressants will be discussed. Furthermore, the effects ofSERT gene polymorphisms on antidepressant efficacy will be examined. Finally, a brief overview of other hypotheses of depression will be addressed as well as factors that must be considered for future antidepressant development.


SSRIs antidepressant serotonin transporter depression reuptake 


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Copyright information

© American Association of Pharmaceutical Scientists 2005

Authors and Affiliations

  • Kellie J. White
    • 1
  • Crystal C. Walline
    • 1
  • Eric L. Barker
    • 1
  1. 1.Dept. of Medicinal Chemistry and Molecular PharmacologyPurdue University School of PharmacyWest Lafayette

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