Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator?
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/169147 |
Resumo: | Sertraline (Zoloft) and fluoxetine (Prozac) are selective serotonin reuptake inhibitors whose antidepressant mechanism of action is classically attributed to an elevation of the extracellular levels of serotonin in the synaptic cleft. However, the biological effects of these drugs seem to be more complex than their traditionally described mechanism of action. Among their actions is the inhibition of different types of Naþ and Kþ channels, as well as of glutamate uptake activity. The clearance of extracellular glutamate is essential to maintain the central nervous system within physiological conditions, and this excitatory neurotransmitter is removed from the synaptic cleft by astrocyte transporters. This transport depends upon a hyperpolarized membrane potential in astrocytes that is mainly maintained by Kir4.1 Kþ channels. The impairment of the Kir4.1 channel activity reduces driving force for the glutamate transporter, resulting in an accumulation of extracellular glutamate. It has been shown that sertraline and fluoxetine inhibit Kir4.1 Kþ channels. Recently, we demonstrated that sertraline reduces glutamate uptake in human platelets, which contain a high-affinity Naþ-dependent glutamate uptake system, with kinetic and pharmacological properties similar to astrocytes in the central nervous system. Considering these similarities between human platelets and astrocytes, one might ask if sertraline could potentially reduce glutamate clearance in the synaptic cleft and consequently modulate glutamatergic transmission. This possibility merits investigation, since it may provide additional information regarding the mechanism of action and perhaps the side effects of these antidepressants. |
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Frizzo, Marcos Emilio dos Santos2017-10-06T02:29:49Z20170011-393Xhttp://hdl.handle.net/10183/169147001048169Sertraline (Zoloft) and fluoxetine (Prozac) are selective serotonin reuptake inhibitors whose antidepressant mechanism of action is classically attributed to an elevation of the extracellular levels of serotonin in the synaptic cleft. However, the biological effects of these drugs seem to be more complex than their traditionally described mechanism of action. Among their actions is the inhibition of different types of Naþ and Kþ channels, as well as of glutamate uptake activity. The clearance of extracellular glutamate is essential to maintain the central nervous system within physiological conditions, and this excitatory neurotransmitter is removed from the synaptic cleft by astrocyte transporters. This transport depends upon a hyperpolarized membrane potential in astrocytes that is mainly maintained by Kir4.1 Kþ channels. The impairment of the Kir4.1 channel activity reduces driving force for the glutamate transporter, resulting in an accumulation of extracellular glutamate. It has been shown that sertraline and fluoxetine inhibit Kir4.1 Kþ channels. Recently, we demonstrated that sertraline reduces glutamate uptake in human platelets, which contain a high-affinity Naþ-dependent glutamate uptake system, with kinetic and pharmacological properties similar to astrocytes in the central nervous system. Considering these similarities between human platelets and astrocytes, one might ask if sertraline could potentially reduce glutamate clearance in the synaptic cleft and consequently modulate glutamatergic transmission. This possibility merits investigation, since it may provide additional information regarding the mechanism of action and perhaps the side effects of these antidepressants.application/pdfengCurrent Therapeutic Research: clinican and experimental. New York, NY. Vol. 87, (2017), p. 9-12SerotoninaReceptor NMDAAntidepressivosGlutamate modulatorZoloftProzacKir4.1 potassium channelsSertralineFluoxetineCan a selective serotonin reuptake inhibitor act as a glutamatergic modulator?Estrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001048169.pdf001048169.pdfTexto completo (inglês)application/pdf241204http://www.lume.ufrgs.br/bitstream/10183/169147/1/001048169.pdf70e58bbfed7ef2e9df594b3f4e5c04b9MD51TEXT001048169.pdf.txt001048169.pdf.txtExtracted Texttext/plain26752http://www.lume.ufrgs.br/bitstream/10183/169147/2/001048169.pdf.txta8779099761372f3db5b530f013a2969MD52THUMBNAIL001048169.pdf.jpg001048169.pdf.jpgGenerated Thumbnailimage/jpeg2040http://www.lume.ufrgs.br/bitstream/10183/169147/3/001048169.pdf.jpg548eba31ebd77da922f7314ace6c5d1bMD5310183/1691472018-10-29 08:34:52.365oai:www.lume.ufrgs.br:10183/169147Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2018-10-29T11:34:52Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator? |
title |
Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator? |
spellingShingle |
Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator? Frizzo, Marcos Emilio dos Santos Serotonina Receptor NMDA Antidepressivos Glutamate modulator Zoloft Prozac Kir4.1 potassium channels Sertraline Fluoxetine |
title_short |
Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator? |
title_full |
Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator? |
title_fullStr |
Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator? |
title_full_unstemmed |
Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator? |
title_sort |
Can a selective serotonin reuptake inhibitor act as a glutamatergic modulator? |
author |
Frizzo, Marcos Emilio dos Santos |
author_facet |
Frizzo, Marcos Emilio dos Santos |
author_role |
author |
dc.contributor.author.fl_str_mv |
Frizzo, Marcos Emilio dos Santos |
dc.subject.por.fl_str_mv |
Serotonina Receptor NMDA Antidepressivos |
topic |
Serotonina Receptor NMDA Antidepressivos Glutamate modulator Zoloft Prozac Kir4.1 potassium channels Sertraline Fluoxetine |
dc.subject.eng.fl_str_mv |
Glutamate modulator Zoloft Prozac Kir4.1 potassium channels Sertraline Fluoxetine |
description |
Sertraline (Zoloft) and fluoxetine (Prozac) are selective serotonin reuptake inhibitors whose antidepressant mechanism of action is classically attributed to an elevation of the extracellular levels of serotonin in the synaptic cleft. However, the biological effects of these drugs seem to be more complex than their traditionally described mechanism of action. Among their actions is the inhibition of different types of Naþ and Kþ channels, as well as of glutamate uptake activity. The clearance of extracellular glutamate is essential to maintain the central nervous system within physiological conditions, and this excitatory neurotransmitter is removed from the synaptic cleft by astrocyte transporters. This transport depends upon a hyperpolarized membrane potential in astrocytes that is mainly maintained by Kir4.1 Kþ channels. The impairment of the Kir4.1 channel activity reduces driving force for the glutamate transporter, resulting in an accumulation of extracellular glutamate. It has been shown that sertraline and fluoxetine inhibit Kir4.1 Kþ channels. Recently, we demonstrated that sertraline reduces glutamate uptake in human platelets, which contain a high-affinity Naþ-dependent glutamate uptake system, with kinetic and pharmacological properties similar to astrocytes in the central nervous system. Considering these similarities between human platelets and astrocytes, one might ask if sertraline could potentially reduce glutamate clearance in the synaptic cleft and consequently modulate glutamatergic transmission. This possibility merits investigation, since it may provide additional information regarding the mechanism of action and perhaps the side effects of these antidepressants. |
publishDate |
2017 |
dc.date.accessioned.fl_str_mv |
2017-10-06T02:29:49Z |
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2017 |
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Estrangeiro info:eu-repo/semantics/article |
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http://hdl.handle.net/10183/169147 |
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0011-393X |
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001048169 |
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http://hdl.handle.net/10183/169147 |
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eng |
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eng |
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Current Therapeutic Research: clinican and experimental. New York, NY. Vol. 87, (2017), p. 9-12 |
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openAccess |
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