ArticleNaunyn-Schmiedeberg's archives of pharmacology2008
The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis 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
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.Alimentary pharmacology & therapeutics · 2012Pooled it
- Prokinetic drugs that stimulate 5-HTNaunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Tegaserod Stimulates 5-HTInternational journal of molecular sciences · 2024Article
- The 5HT4R agonist velusetrag efficacy on neuropathic chronic intestinal pseudo-obstruction in PrP-SCA7-92Q transgenic mice.Frontiers in pharmacology · 2024Article
- Current Opinion on Prucalopride in Gastroparesis and Chronic Constipation Treatment: A Focus on Patient Selection and Safety.Therapeutics and clinical risk management · 2021Review
- Gastroparesis and Functional Dyspepsia: A Blurring Distinction of Pathophysiology and Treatment.Journal of neurogastroenterology and motility · 2019Review
- Cardiovascular safety of prokinetic agents: A focus on drug-induced arrhythmias.Neurogastroenterology and motility · 2018Review
- The novel, potent and highly selective 5-HTBritish journal of pharmacology · 2018Article
- Diabetic gastroparesis: current challenges and future prospects.Clinical and experimental gastroenterology · 2018Review
- A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research.Frontiers in pharmacology · 2018Review
- New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond.World journal of gastroenterology · 2017Review
- Patient considerations in the management of chronic constipation: focus on prucalopride.Patient preference and adherence · 2016Review
- Current developments in pharmacological therapeutics for chronic constipation.Acta pharmaceutica Sinica. B · 2015Review
- Treatment of Chronic Constipation: Prescription Medications and Surgical Therapies.Gastroenterology & hepatology · 2015Article
- Tegaserod mimics the neurostimulatory glycan polysialic acid and promotes nervous system repair.Neuropharmacology · 2014Article
- The in vitro pharmacological profile of TD-1211, a neutral opioid receptor antagonist.Naunyn-Schmiedeberg's archives of pharmacology · 2013Article
- The inability of tegaserod to affect platelet aggregation and coronary artery tone at supratherapeutic concentrations.Naunyn-Schmiedeberg's archives of pharmacology · 2012Article
- New treatment options for chronic constipation: mechanisms, efficacy and safety.Canadian journal of gastroenterology = Journal canadien de gastroenterologie · 2011Review
- The Pharmacology of TD-8954, a Potent and Selective 5-HT(4) Receptor Agonist with Gastrointestinal Prokinetic Properties.Frontiers in pharmacology · 2011Article
- Challenges and prospects for pharmacotherapy in functional gastrointestinal disorders.Therapeutic advances in gastroenterology · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The in vitro pharmacological profile of TD-5108, a novel, selective 5-HT(4) receptor agonist, was compared to that of clinically efficacious gastroprokinetic 5-HT(4) receptor agonists. TD-5108 produced an elevation of cyclic adenosine monophosphate in human embryonic kidney 293 cells expressing the human recombinant 5-HT(4(c)) (h5-HT(4(c))) receptor (pEC(50) = 8.3) and 5-HT(4) receptor-mediated relaxation of the rat esophagus (pEC(50) = 7.9) and contraction of the guinea pig colon (pEC(50) = 7.9). In all in vitro assays, TD-5108 was a high intrinsic activity agonist, unlike tegaserod, mosapride, and cisapride which, in the majority of test systems, had lower intrinsic activity. TD-5108 had high affinity (pK (i) = 7.7) and selectivity (> or =25-fold) for h5-HT(4(c)) receptors over other biogenic amine receptors. TD-5108 was >500-fold selective over other 5-HT receptors (including h5-HT(2B) and h5-HT(3A)) and, at 3 microM, had no effect on human ether-à-go-go-related gene K+ channels. In conclusion, TD-5108 is a selective 5-HT(4) receptor agonist in vitro. The high intrinsic activity and preferential binding of TD-5108 to 5-HT4 over other 5-HT receptors may result in an improved clinical profile for the treatment of gastrointestinal disorders of reduced motility.
Indexed as
Identifiers
18415081What 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.