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
-
Investigating the Effect of Cognitive-behavioral Stress Management on Occupational Performance among Women with Breast Cancer
Current Women`s Health Reviews Evidence of 2 Populations of Mephedrone Abusers by Hair Testing. Application to 4 Forensic Expertises
Current Neuropharmacology Physiology, Affecting Factors and Strategies for Control of Pig Meat Intramuscular Fat
Recent Patents on Food, Nutrition & Agriculture Suicide and Suicide Attempts in Elderly Patients: An Epidemiological Analysis of Risk Factors and Prevention
Current Pharmaceutical Design Huntingtin Levels are Elevated in Hippocampal Post-Mortem Samples of Alzheimer’s Disease Brain
Current Alzheimer Research Anti-Infective and Anti-Tumor Agents Based on the Depletion of Immune Suppressive Effects
Current Medicinal Chemistry Effects of Secondhand Smoke on Thyroid Function
Inflammation & Allergy - Drug Targets (Discontinued) Editorial [Hot Topic: Pharmacological Treatments of Alcohol and Drug Addiction: Whats New? (Executive Guest Editor: Laurent Karila)]
Current Pharmaceutical Design Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development
Current Topics in Medicinal Chemistry Valproic Acid Metabolism and its Consequences on Sexual Functions
Current Drug Metabolism Potential Roles of Selenium and Selenoproteins in the Prevention of Alzheimer's Disease
Current Topics in Medicinal Chemistry Genetics of Cancer Susceptibility
Current Genomics Pharmacological Manipulation of the Vasoconstrictive Effects of Amyloid- β Peptides by Donepezil and Rivastigmine
Current Alzheimer Research Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential
Current Pharmaceutical Design Editorial [Hot topic: Models and Evolution of Inflammatory Activities (Executive Editor: Giuseppe Scapigliati)]
Current Pharmaceutical Design Determination of Lipoic Acid in the form of 2-S-pyridinium Derivative by High-performance Liquid Chromatography with Ultraviolet Detection
Current Analytical Chemistry MCP-1/CCL2 as a Therapeutic Target in Myocardial Infarction and Ischemic Cardiomyopathy
Inflammation & Allergy - Drug Targets (Discontinued) Primary Antiphospholipid Syndrome and Pulmonary Hypertension
Current Pharmaceutical Design Depot Based Drug Delivery System for the Management of Depression
Current Drug Delivery Monoamine Oxidase Inhibitors Extracted from Tobacco Smoke as Neuroprotective Factors for Potential Treatment of Parkinson`s Disease
CNS & Neurological Disorders - Drug Targets