Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport

Abstract Citalopram prevents serotonin (5-HT) uptake into platelets by blocking the serotonin reuptake transporter (SERT). Although some clinical data suggest that selective serotonin reuptake inhibitors (SSRIs) may affect haemostasis and thrombosis, these poorly-characterised effects are not well u...

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Autores principales:	Harvey G. Roweth, Ruoling Yan, Nader H. Bedwani, Alisha Chauhan, Nicole Fowler, Alice H. Watson, Jean-Daniel Malcor, Stewart O. Sage, Gavin E. Jarvis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/03e1a156b5144db0b5daf6945d11679e
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spelling	oai:doaj.org-article:03e1a156b5144db0b5daf6945d11679e2021-12-02T15:08:24ZCitalopram inhibits platelet function independently of SERT-mediated 5-HT transport10.1038/s41598-018-21348-32045-2322https://doaj.org/article/03e1a156b5144db0b5daf6945d11679e2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21348-3https://doaj.org/toc/2045-2322Abstract Citalopram prevents serotonin (5-HT) uptake into platelets by blocking the serotonin reuptake transporter (SERT). Although some clinical data suggest that selective serotonin reuptake inhibitors (SSRIs) may affect haemostasis and thrombosis, these poorly-characterised effects are not well understood mechanistically and useful in vitro data is limited. We sought to determine whether the inhibitory effects of citalopram on platelets are mediated via its pharmacological inhibition of 5-HT transport. We quantified the inhibitory potency of (RS)-, (R)- and (S)-citalopram on platelet function. If SERT blockade is the primary mechanism for citalopram-mediated platelet inhibition, these potencies should show quantitative congruence with inhibition of 5-HT uptake. Our data show that citalopram inhibits platelet aggregation, adhesion and thromboxane production with no difference in potency between (R)- and (S)-isomers. By contrast, citalopram had a eudysmic ratio of approximately 17 (S > R) for SERT blockade. Furthermore, nanomolar concentrations of citalopram inhibited 5-HT uptake into platelets but had no effect on other platelet functions, which were inhibited by micromolar concentrations. Our data indicate that citalopram-induced inhibition of platelets in vitro is not mediated by blockade of 5-HT transport. This raises a new question for future investigation: by what mechanism(s) does citalopram inhibit platelets?Harvey G. RowethRuoling YanNader H. BedwaniAlisha ChauhanNicole FowlerAlice H. WatsonJean-Daniel MalcorStewart O. SageGavin E. JarvisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Harvey G. Roweth Ruoling Yan Nader H. Bedwani Alisha Chauhan Nicole Fowler Alice H. Watson Jean-Daniel Malcor Stewart O. Sage Gavin E. Jarvis Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport
description	Abstract Citalopram prevents serotonin (5-HT) uptake into platelets by blocking the serotonin reuptake transporter (SERT). Although some clinical data suggest that selective serotonin reuptake inhibitors (SSRIs) may affect haemostasis and thrombosis, these poorly-characterised effects are not well understood mechanistically and useful in vitro data is limited. We sought to determine whether the inhibitory effects of citalopram on platelets are mediated via its pharmacological inhibition of 5-HT transport. We quantified the inhibitory potency of (RS)-, (R)- and (S)-citalopram on platelet function. If SERT blockade is the primary mechanism for citalopram-mediated platelet inhibition, these potencies should show quantitative congruence with inhibition of 5-HT uptake. Our data show that citalopram inhibits platelet aggregation, adhesion and thromboxane production with no difference in potency between (R)- and (S)-isomers. By contrast, citalopram had a eudysmic ratio of approximately 17 (S > R) for SERT blockade. Furthermore, nanomolar concentrations of citalopram inhibited 5-HT uptake into platelets but had no effect on other platelet functions, which were inhibited by micromolar concentrations. Our data indicate that citalopram-induced inhibition of platelets in vitro is not mediated by blockade of 5-HT transport. This raises a new question for future investigation: by what mechanism(s) does citalopram inhibit platelets?
format	article
author	Harvey G. Roweth Ruoling Yan Nader H. Bedwani Alisha Chauhan Nicole Fowler Alice H. Watson Jean-Daniel Malcor Stewart O. Sage Gavin E. Jarvis
author_facet	Harvey G. Roweth Ruoling Yan Nader H. Bedwani Alisha Chauhan Nicole Fowler Alice H. Watson Jean-Daniel Malcor Stewart O. Sage Gavin E. Jarvis
author_sort	Harvey G. Roweth
title	Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport
title_short	Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport
title_full	Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport
title_fullStr	Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport
title_full_unstemmed	Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport
title_sort	citalopram inhibits platelet function independently of sert-mediated 5-ht transport
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/03e1a156b5144db0b5daf6945d11679e
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Citalopram inhibits platelet function independently of SERT-mediated 5-HT transport

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