SynthesisAlimentary pharmacology & therapeutics2012
Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.
Synthesis in Alimentary pharmacology & therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 271 citations in OpenAlex.
- Prokinetics for the treatment of functional dyspepsia: Bayesian network meta-analysis.BMC gastroenterology · 2017Pooled it
- Use of Prucalopride for Chronic Constipation: A Systematic Review and Meta-analysis of Published Randomized, Controlled Trials.Journal of neurogastroenterology and motility · 2016Pooled it
- Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis.World journal of gastroenterology · 2014Pooled it
- Clinical Trial: Efficacy and Safety of Velusetrag in Chronic Intestinal Pseudo-Obstruction: A Randomized, Phase 2, Placebo-Controlled, Crossover, Multiple (n = 1), Proof-of-Concept Study.Neurogastroenterology and motility · 2026Trial
- A population pharmacokinetic-pharmacodynamic model of YH12852, a highly selective 5-hydroxytryptamine 4 receptor agonist, in healthy subjects and patients with functional constipation.CPT: pharmacometrics & systems pharmacology · 2021Trial
- YH12852, a Potent and Selective Receptor Agonist of 5-hydroxytryptamine, Increased Gastrointestinal Motility in Healthy Volunteers and Patients With Functional Constipation.Clinical and translational science · 2021Trial
- Blinded, Double-Dummy, Parallel-Group, Phase 2a Randomized Clinical Trial to Evaluate the Efficacy and Safety of a Highly Selective 5-Hydroxytryptamine Type 4 Receptor Agonist in Critically Ill Patients With Enteral Feeding Intolerance.JPEN. Journal of parenteral and enteral nutrition · 2021Trial
- Preliminary safety and efficacy profile of prucalopride in the treatment of systemic sclerosis (SSc)-related intestinal involvement: results from the open label cross-over PROGASS study.Arthritis research & therapy · 2017Trial
- Depression in neurodegenerative disease: neurobiological mechanisms and emerging treatments.Molecular psychiatry · 2026Review
- Gastroparesis in Parkinson's disease: Diagnostic and clinical implications for optimizing pharmacological treatment.Journal of Parkinson's disease · 2026Review
- Irritable bowel syndrome management: current insights.Singapore medical journal · 2026Article
- Pharmacovigilance Due Diligence in Drug Development: A Practical Playbook for Risk Identification, Compliance Assessment, and Strategic Decision Making.Drug safety · 2026Review
- Impact of itopride on functional dyspepsia symptom progression: a multicenter noninterventional postregistration study.Therapeutic advances in gastroenterology · 2026Article
- Recent Developments in Oral Drug Delivery of Prokinetic Agents: Nanoparticles and Beyond.Current drug delivery · 2026Review
- Targeting Irritable Bowel Syndrome Through Diet and Mechanism-Based Therapies: A Pathophysiological Approach.Nutrients · 2025Review
- Clebopride stimulates 5-HTNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Ten-Year Trends in Pharmacologic Management of Gastroesophageal Reflux Disease and Pediatric Feeding Disorders in Young Children.The Journal of pediatrics · 2025Article
- 2025 Seoul Consensus on Clinical Practice Guidelines for Irritable Bowel Syndrome.Journal of neurogastroenterology and motility · 2025Review
- [Pharmacologic Treatment of Irritable Bowel Syndrome with Predominant Constipation].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2025Review
- Pharmacologic treatments for gastroparesis.Pharmacological reviews · 2025Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
11 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs).
aimTo 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.
methodsArticles 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.
resultsRetrieved 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).
conclusions5-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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.