ArticleFrontiers in pharmacology2011
The Pharmacology of TD-8954, a Potent and Selective 5-HT(4) Receptor Agonist with Gastrointestinal Prokinetic Properties.
Article in Frontiers in pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- The Effect of Hepatic Impairment on the Pharmacokinetics of Intravenously Administered Felcisetrag (TAK-954).Journal of clinical pharmacology · 2022Trial
- Randomised study: effects of the 5-HTAlimentary pharmacology & therapeutics · 2021Trial
- Felcisetrag stimulates 5-HTNaunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Pharmacologic treatments for gastroparesis.Pharmacological reviews · 2025Review
- The Use of Pre-Endoscopic Metoclopramide Does Not Prevent the Need for Repeat Endoscopy: A U.S. Based Retrospective Cohort Study.Life (Basel, Switzerland) · 2024Article
- Diabetic gastroparesis: clinical features, diagnosis and management.Irish journal of medical science · 2023Review
- Clinical and Nonclinical Disposition and In Vitro Drug-Drug Interaction Potential of Felcisetrag, a Highly Selective and Potent 5-HTEuropean journal of drug metabolism and pharmacokinetics · 2022Article
- Rational Design, Chemical Syntheses, and Biological Evaluations of Peripherally Selective Mu Opioid Receptor Ligands as Potential Opioid Induced Constipation Treatment.Journal of medicinal chemistry · 2022Article
- New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders.Gastroenterology · 2021Review
- Good to Know: Baseline Data on Feed Intake, Fecal Pellet Output and Intestinal Transit Time in Guinea Pig as a Frequently Used Model in Gastrointestinal Research.Animals : an open access journal from MDPI · 2021Article
- New Developments in Prokinetic Therapy for Gastric Motility Disorders.Frontiers in pharmacology · 2021Review
- Postoperative Ileus and Postoperative Gastrointestinal Tract Dysfunction: Pathogenic Mechanisms and Novel Treatment Strategies Beyond Colorectal Enhanced Recovery After Surgery Protocols.Frontiers in pharmacology · 2020Review
- A quantitative systems pharmacology model of colonic motility with applications in drug development.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- The novel, potent and highly selective 5-HTBritish journal of pharmacology · 2018Article
- Current developments in pharmacological therapeutics for chronic constipation.Acta pharmaceutica Sinica. B · 2015Review
- Early investigational therapeutics for gastrointestinal motility disorders: from animal studies to Phase II trials.Expert opinion on investigational drugs · 2015Review
- Should we stop prescribing metoclopramide as a prokinetic drug in critically ill patients?Critical care (London, England) · 2014Review
- The in vivo pharmacodynamics of the novel opioid receptor antagonist, TD-1211, in models of opioid-induced gastrointestinal and CNS activity.Naunyn-Schmiedeberg's archives of pharmacology · 2013Article
- Drug development for the irritable bowel syndrome: current challenges and future perspectives.Frontiers in pharmacology · 2013Article
- Novel insights which may translate into treatments for irritable bowel syndrome.Frontiers in pharmacology · 2013Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study evaluated the in vitro and in vivo pharmacological properties of TD-8954, a potent and selective 5-HT(4) receptor agonist. TD-8954 had high affinity (pK(i) = 9.4) for human recombinant 5-HT(4(c)) (h5-HT(4(c))) receptors, and selectivity (>2,000-fold) over all other 5-hydroxytryptamine (5-HT) receptors and non-5-HT receptors, ion channels, enzymes and transporters tested (n = 78). TD-8954 produced an elevation of cAMP in HEK-293 cells expressing the h5-HT(4(c)) receptor (pEC(50) = 9.3), and contracted the guinea pig colonic longitudinal muscle/myenteric plexus preparation (pEC(50) = 8.6). TD-8954 had moderate intrinsic activity in the in vitro assays. In conscious guinea pigs, subcutaneous administration of TD-8954 (0.03-3 mg/kg) increased the colonic transit of carmine red dye, reducing the time taken for its excretion. Following intraduodenal dosing to anesthetized rats, TD-8954 (0.03-10 mg/kg) evoked a dose-dependent relaxation of the esophagus. Following oral administration to conscious dogs, TD-8954 (10 and 30 μg/kg) produced an increase in contractility of the antrum, duodenum, and jejunum. In a single ascending oral dose study in healthy human subjects, TD-8954 (0.1-20 mg) increased bowel movement frequency and reduced the time to first stool. It is concluded that TD-8954 is a potent and selective 5-HT(4) receptor agonist in vitro, with robust in vivo stimulatory activity in the gastrointestinal (GI) tract of guinea pigs, rats, dogs, and humans. TD-8954 may have clinical utility in patients with disorders of reduced GI motility.
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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.