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
Current Signal Transduction Therapy
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/157436209788167538 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
PREFACE
Current Neuropharmacology Modulation of Inducible Nitric Oxide Synthase Activation by Immuno-suppressive Drugs
Current Drug Metabolism Prospects for miR-21 as a Target in the Treatment of Lung Diseases
Current Pharmaceutical Design Investigating Physical, Psychological and Social Well-being of Older Persons in Jordan
Current Aging Science Cytokines as a Precipitant of Depressive Illness: Animal and Human Studies
Current Pharmaceutical Design Possible Physiopathological Roles of the Transglutaminase Activity in the Etiopathogenesis of Human Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Synthesis, Cytotoxic Evaluation, Docking and QSAR Study of N-(4-Oxo- 2-(4-((5-Aryl-1,3,4-Thiadiazol-2-yl)Amino)Phenyl)Thiazolidin-3-yl) Benzamides as Antitubulin Agents
Current Topics in Medicinal Chemistry A Review of Clinical Pharmacokinetics and Pharmacodynamics of Galantamine, a Reversible Acetylcholinesterase Inhibitor for the Treatment of Alzheimer s Disease, in Healthy Subjects and Patients
Current Clinical Pharmacology Pharmacokinetics of Ceftriaxone in Carbontetrachloride-Induced Hepatopathic and Uranyl nitrate-Induced Nephropathic Goats Following Single Dose Intravenous Administration
Drug Metabolism Letters Microwave Induced Center-Doping of Transition Metals Ions in Aqueous CdS NCs with Special Optical Properties
Current Microwave Chemistry Unravelling the Role of Infectious Agents in the Pathogenesis of Human Autoimmunity: The Hypothesis of the Retroviral Involvement Revisited
Current Molecular Medicine Biological Properties of Yeast-based Mannoprotein for Prospective Biomedical Applications
Combinatorial Chemistry & High Throughput Screening Gastrodia Elata Bl Attenuates Cocaine-Induced Conditioned Place Preference and Convulsion, but not Behavioral Sensitization in Mice: Importance of GABAA Receptors
Current Neuropharmacology Role of Androgens in Womens Sexual Function & Dysfunction: What Have We Learned in Six Decades?
Current Women`s Health Reviews Meet Our Associate Editor
Current Alzheimer Research Novel Perspectives in Celiac Disease Therapy
Mini-Reviews in Medicinal Chemistry Recent Advances and Challenges of the Drugs Acting on Monoamine Transporters
Current Medicinal Chemistry FTY720: A Most Promising Immunosuppressant Modulating Immune Cell Functions
Mini-Reviews in Medicinal Chemistry Neuropathic Pain: Models and Mechanisms
Current Pharmaceutical Design Functional Magnetic Resonance Imaging in Abstinent MDMA Users: A Review
Current Drug Abuse Reviews