The DOI matches its Crossref record; 214 of the 214 references it cites were found in a registry or an index.
Systematic review: cardiovascular safety profile of 5‐ HT 4 agonists developed for gastrointestinal disorders
Open accessAbstract
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UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data.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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“nonselective 5-HT4 agonists have been linked to a greater frequency of cardiovascular adverse events in clinical trials”
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Gastroparesis: a turning point in understanding and treatment
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Self-citationPrucalopride in Gastroparesis: A Randomized Placebo-Controlled Crossover Study
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Self-citationSerotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders
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Metadata
- Authors
- Tack, J., Camilleri, M., Chang, L., Chey, W. D., Galligan, J. J., Lacy, B. E., Müller‐Lissner, S., Quigley, E. M. M., Schuurkes, J., De Maeyer, J. H., & Stanghellini, V.
- Affiliations
- KU Leuven (BE)
- Mayo Clinic (US)
- University of California, Los Angeles (US)
- Michigan Medicine (US)
- Michigan State University (US)
- Dartmouth–Hitchcock Medical Center (US)
- Department of Internal Medicine, Park‐Klinik Weissensee Berlin Germany
- University College Cork (IE)
- Shire‐Movetis NV Turnhout Belgium
- University of Bologna (IT)
- Corresponding author
- Tack, J.
- ORCID
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2012-02-22
- Volume
- 35
- Issue
- 7
- Pages
- 745-767
- ISSN
- 0269-2813 (ISSN-L)
- 1365-2036
- PMC
- PMC3491670
- OpenAlex
- W2075335843
- Cited by
- 286
- References
- 214
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 11 · 2023: 7 · 2022: 15 · 2021: 30 · 2020: 24 · 2019: 16 · 2018: 21 · 2017: 23 · 2016: 30 · 2015: 20 · 2014: 29 · 2013: 18 · 2012: 11
- FWCI
- 3.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alimentary Pharmacology & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Funders
- Falk Foundation
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Ikaria
- Danone
- Ironwood Pharmaceuticals, Incorporated
- Novo Nordisk
- Astellas Pharma
- Ipsen
- Norgine
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Keywords
- 5-HT4 receptor agonist, cardiovascular safety, cisapride, tegaserod, prucalopride, clebopride, mosapride, renzapride, QT prolongation, myocardial ischemia, hERG, gastrointestinal motility disorders, drug selectivity, adverse drug reactions
- MeSH terms
- Cardiovascular Diseases, Gastrointestinal Agents, Gastrointestinal Diseases, Humans, Indoles, Randomized Controlled Trials as Topic, Cisapride, Serotonin 5-HT4 Receptor Agonists
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