Abstract
Since the initial observations linking 5-HT to psychiatric illness, evidence for a role of 5-HT and, in particular, a decreased brain serotonergic function in the pathology of a plethora of related disorders, has grown. However, it is the role of 5-HT in the pathogenesis of anxiety disorders and depression and the mechanism of action of antidepressants which has received the most attention. Thus enhanced serotonergic neurotransmission has become one of the unifying mechanisms of action of modern day antidepressants / anxiolytics such as monoamine oxidase inhibitors, tricyclic antidepressants, and serotonin reuptake inhibitors. Interestingly all of these treatments are associated with a delay to therapeutic efficacy and in some cases treatment resistance, despite immediate enhancements in serotonergic neurotransmission. The postulated reason for this is the need for temporal neuroplastic changes in the control of serotonergic neurotransmission, and more specifically changes in 5-HT1 autoreceptor function. Thus significant research has gone into pharmacologically targeting these 5-HT1 autoreceptors as a means of augmenting the efficacy of current therapeutic mechanisms. Here we will review the rationale behind the various augmentation strategies adopted and the progress made in identifying novel therapeutics for conditions such as depression and anxiety disorders.
Keywords: Serotonin (5-HT), serotonin transporter (SERT), serotonin specific reuptake inhibitor (SSRI), 5-HT1A, 5-HT1B, 5-HT1D, autoreceptor, add-on, depression, anxiety
Current Topics in Medicinal Chemistry
Title: 5-HT1 Receptor Augmentation Strategies as Enhanced Efficacy Therapeutics for Psychiatric Disorders
Volume: 8 Issue: 12
Author(s): Lee A. Dawson and Steve M. Bromidge
Affiliation:
Keywords: Serotonin (5-HT), serotonin transporter (SERT), serotonin specific reuptake inhibitor (SSRI), 5-HT1A, 5-HT1B, 5-HT1D, autoreceptor, add-on, depression, anxiety
Abstract: Since the initial observations linking 5-HT to psychiatric illness, evidence for a role of 5-HT and, in particular, a decreased brain serotonergic function in the pathology of a plethora of related disorders, has grown. However, it is the role of 5-HT in the pathogenesis of anxiety disorders and depression and the mechanism of action of antidepressants which has received the most attention. Thus enhanced serotonergic neurotransmission has become one of the unifying mechanisms of action of modern day antidepressants / anxiolytics such as monoamine oxidase inhibitors, tricyclic antidepressants, and serotonin reuptake inhibitors. Interestingly all of these treatments are associated with a delay to therapeutic efficacy and in some cases treatment resistance, despite immediate enhancements in serotonergic neurotransmission. The postulated reason for this is the need for temporal neuroplastic changes in the control of serotonergic neurotransmission, and more specifically changes in 5-HT1 autoreceptor function. Thus significant research has gone into pharmacologically targeting these 5-HT1 autoreceptors as a means of augmenting the efficacy of current therapeutic mechanisms. Here we will review the rationale behind the various augmentation strategies adopted and the progress made in identifying novel therapeutics for conditions such as depression and anxiety disorders.
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Cite this article as:
Dawson A. Lee and Bromidge M. Steve, 5-HT1 Receptor Augmentation Strategies as Enhanced Efficacy Therapeutics for Psychiatric Disorders, Current Topics in Medicinal Chemistry 2008; 8 (12) . https://dx.doi.org/10.2174/156802608785161439
DOI https://dx.doi.org/10.2174/156802608785161439 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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