Therapeutic Relevance of the Allosteric Modulation of the 5-HT Transporter

Title: Therapeutic Relevance of the Allosteric Modulation of the 5-HT Transporter

Volume: 4 Issue: 2

Author(s): Ouissame Mnie-Filali, Mostafa El Mansari, Connie Sanchez and Nasser Haddjeri

Affiliation:

Keywords: Enantiomers, escitalopram, R-citalopram, serotonin transporter, allosteric modulation, protein kinase C, conformational modification

Abstract: The serotonin (5-HT) transporter (SERT) is implicated in numerous neuropsychiatric disorders including major depression and represents the main target for antidepressants, especially for the selective serotonin reuptake inhibitors (SSRIs). A recently developed SSRI has the particularity to enhance its own reuptake inhibitory activity via the allosteric modulation of SERT. In this review, the SSRI escitalopram, the (S)-enantiomer of the SSRI citalopram, is exemplified in order to illustrate such an allosteric regulation of SERT and to depict putative biochemical mechanisms involving changes in SERT proteins conformations and/or their cellular distribution that could be linked to this antidepressant specificity. Insights into the physiological mechanisms by which SERT is regulated will increase not only our understanding of pathologic processes underlying affective disorders, but can also lead to the development of new strategies to treat these devastating illnesses.

Cite this article as:

Mnie-Filali Ouissame, Mansari El Mostafa, Sanchez Connie and Haddjeri Nasser, Therapeutic Relevance of the Allosteric Modulation of the 5-HT Transporter, Current Signal Transduction Therapy 2009; 4 (2) . https://dx.doi.org/10.2174/157436209788167538