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Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders

BACKGROUND: The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). AIM: To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a n...

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Autores principales: Tack, J, Camilleri, M, Chang, L, Chey, W D, Galligan, J J, Lacy, B E, Müller-Lissner, S, Quigley, E M M, Schuurkes, J, Maeyer, J H, Stanghellini, V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491670/
https://www.ncbi.nlm.nih.gov/pubmed/22356640
http://dx.doi.org/10.1111/j.1365-2036.2012.05011.x
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author Tack, J
Camilleri, M
Chang, L
Chey, W D
Galligan, J J
Lacy, B E
Müller-Lissner, S
Quigley, E M M
Schuurkes, J
Maeyer, J H
Stanghellini, V
author_facet Tack, J
Camilleri, M
Chang, L
Chey, W D
Galligan, J J
Lacy, B E
Müller-Lissner, S
Quigley, E M M
Schuurkes, J
Maeyer, J H
Stanghellini, V
author_sort Tack, J
collection PubMed
description BACKGROUND: The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). AIM: To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. METHODS: Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. RESULTS: Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). CONCLUSIONS: 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility.
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spelling pubmed-34916702012-11-09 Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders Tack, J Camilleri, M Chang, L Chey, W D Galligan, J J Lacy, B E Müller-Lissner, S Quigley, E M M Schuurkes, J Maeyer, J H Stanghellini, V Aliment Pharmacol Ther Systematic Review BACKGROUND: The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). AIM: To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. METHODS: Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. RESULTS: Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). CONCLUSIONS: 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. Blackwell Publishing Ltd 2012-04 2012-02-22 /pmc/articles/PMC3491670/ /pubmed/22356640 http://dx.doi.org/10.1111/j.1365-2036.2012.05011.x Text en Copyright © 2012 Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Systematic Review
Tack, J
Camilleri, M
Chang, L
Chey, W D
Galligan, J J
Lacy, B E
Müller-Lissner, S
Quigley, E M M
Schuurkes, J
Maeyer, J H
Stanghellini, V
Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders
title Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders
title_full Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders
title_fullStr Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders
title_full_unstemmed Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders
title_short Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders
title_sort systematic review: cardiovascular safety profile of 5-ht(4) agonists developed for gastrointestinal disorders
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491670/
https://www.ncbi.nlm.nih.gov/pubmed/22356640
http://dx.doi.org/10.1111/j.1365-2036.2012.05011.x
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