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

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

Journal Name: Current Signal Transduction Therapy

Volume 4 , Issue 2 , 2009

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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.

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

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Article Details

VOLUME: 4
ISSUE: 2
Year: 2009
Page: [82 - 87]
Pages: 6
DOI: 10.2174/157436209788167538
Price: $58

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