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5-HT4 Agonist

The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform

Michael Camilleri – 1st expert on this subject based on the ideXlab platform

  • Emerging pharmacologic therapies for irritable bowel syndrome.
    Current Gastroenterology Reports, 2010
    Co-Authors: Noriaki Manabe, Banny S. Wong, Michael Camilleri

    Abstract:

    New therapies are being developed for irritable bowel syndrome (IBS). These advances are based on understanding pathophysiology or the development of medications with greater selectivity in classes of agents with known efficacy. Prucalopride, the newest European Medicines Agency-approved 5-hydroxytryptamine receptor 4 (5-HT4) Agonist, is effective in the treatment of chronic constipation with improved cardiovascular safety relative to older 5-HT4 drugs; similarly, ramosetron, the 5-hydroxytryptamine receptor 3 (5-HT3) antAgonist, appears efficacious in diarrhea-predominant IBS. Secretagogues with different mechanisms of action target apical domains in enterocytes that are involved in chloride secretion, such as chloride channels, the cystic fibrosis transmembrane regulator, and guanylate cyclase C. As a class, such secretagogues have high efficacy and safety for constipation. With more data obtained from phase 2 and 3 trials, we expect other classes of medications, including bile acid modulators, anti-inflammatory agents, visceral analgesics, and newer centrally acting agents to be efficacious and enter the armamentarium for the treatment of IBS in the future.

  • Role of prucalopride, a serotonin (5-HT4) receptor Agonist, for the treatment of chronic constipation
    Clinical and Experimental Gastroenterology, 2010
    Co-Authors: Banny S. Wong, Noriaki Manabe, Michael Camilleri

    Abstract:

    Constipation affects up to a quarter of the population in developed countries and is associated with poor quality of life and significant economic burden. Many patients with chronic constipation are dissatisfied with current therapy due to lack of long-term efficacy or side effects. Previous nonselective 5-hydroxytryptamine receptor 4 (5-HT4) Agonists have been associated with significant interactions with other receptors (5-HT1B, 5-HT1D, and 5-HT2B for tegaserod; hERG for cisapride), leading to adverse cardiovascular events resulting in withdrawal of these drugs from the market. Prucalopride is a novel gastrointestinal prokinetic agent. It acts as a high affinity, highly-selective 5-HT4 Agonist. Its efficacy in patients with chronic constipation has been demonstrated in several phase II and phase III clinical trials showing significant improvements in bowel transit, bowel function, gastrointestinal symptoms, and quality of life, with benefit maintained for up to 24 months in open label, multicenter, follow-up studies. Prucalopride’s high selectivity for the 5-HT4 receptor may explain its favorable safety and tolerability profiles, even in elderly subjects with stable cardiovascular disease. Prucalopride is a well tolerated and efficacious prokinetic medication that should enhance the treatment of chronic constipation unresponsive to first-line treatments.

  • Stomach Dysfunction in Diabetes Mellitus: Emerging Technology and Pharmacology
    Journal of diabetes science and technology, 2010
    Co-Authors: Lawrence A. Szarka, Michael Camilleri

    Abstract:

    Gastroparesis and other types of gastric dysfunction result in substantial morbidity in diabetes patients. The pathophysiology of these disorders is incompletely understood. This article reviews techniques applicable to the assessment of gastric function in diabetes patients, including the measurement of emptying, accommodation, and contractility. Available treatment options are also reviewed, including novel yet unapproved serotonin 5-HT4 Agonist pharmacological treatments, as well as the role of endoscopic, surgical, and device treatments of gastroparesis.

Jan Tack – 2nd expert on this subject based on the ideXlab platform

  • Tegaserod: a new 5-HT4 Agonist in the treatment of irritable bowel syndrome
    Expert Opinion on Pharmacotherapy, 2020
    Co-Authors: Jan Tack, Maura Corsetti

    Abstract:

    Tegaserod is a selective partial Agonist acting on serotonergic type 4 receptors (5-HT4). Pharmacodynamic studies indicate that tegaserod is able to stimulate gut propulsion and secretion with a net prokinetic effect. In contrast to other 5-HT4 Agonists endowed with a complex pharmacological profile, tegaserod has a reliable prokinetic activity in the colon. Clinical trials show that tegaserod is effective and safe in the treatment of patients with irritable bowel syndrome. In particular, tegaserod relieves symptoms of abdominal pain, discomfort, abdominal bloating and constipation.

  • Randomised clinical trial: the 5-HT4 Agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy.
    Alimentary Pharmacology & Therapeutics, 2015
    Co-Authors: Nicholas J. Shaheen, Jan Tack, Philip B. Miner, J Adler, S. Dedrie, D. A. Johnson, Peter Malfertheiner, A. Meulemans, L Poole, L. Thielemans

    Abstract:

    Summary

    Background

    A substantial proportion of patients with gastro-oesophageal reflux disease (GERD) have only a partial response to proton pump inhibitor (PPI) therapy. Prokinetic drugs may improve reflux symptoms by enhancing oesophageal motility and gastric emptying.

    Aim

    To evaluate the effect of revexepride, a novel prokinetic 5-hydroxytryptamine type 4 (5-HT4) receptor Agonist, compared with placebo, in patients with GERD who have a partial response to PPIs.

    Methods

    A phase 2b, double-blind, parallel-group study was conducted, in which patients were randomised to one of three revexepride treatment groups (0.1, 0.5 and 2.0 mg three times daily) or placebo (1:1:1:1 ratio). Daily e-diary data captured patients’ symptoms over an 8-week treatment period. The primary efficacy outcome was the weekly percentage of regurgitation-free days in the second half of the study (weeks 5–8).

    Results

    In total, 480 patients were randomised and 477 received treatment (mean age 47.9 years; 61% women). The mean percentage of regurgitation-free days increased from baseline (range, 15.0–18.8%) to week 8 (62.3–70.5%) in all four study arms; however, there were no statistically significant differences in this change between placebo and the three treatment arms. No dose-dependent relationship in treatment effect was observed for any of the study endpoints. The incidence of treatment-emergent adverse events (TEAEs) was revexepride dose-dependent. Only one serious TEAE occurred and none resulted in death.

    Conclusions

    Revexepride was no more effective than placebo in controlling regurgitation in patients with GERD symptoms partially responsive to PPIs. Revexepride was well tolerated. ClinicalTrials.gov Identifier: NCT01472939.

  • Current and future therapies for chronic constipation
    Best Practice & Research in Clinical Gastroenterology, 2011
    Co-Authors: Jan Tack

    Abstract:

    In this article, traditional and novel therapies for chronic constipation are reviewed. Traditional laxatives are effective at inducing bowel movements, but efficacy in long-term management and efficacy on constipation-associated abdominal symptoms are less well established, with the exception of polyethylene glycol, for which long-term studies confirm sustained efficacy. Recently approved drugs include the colonic secretagogue lubiprostone and the 5-HT4 Agonist prucalopride. In controlled trials in chronic constipation, these drugs were shown to significantly improve constipation and its associated symptoms, with a favourable safety record. Methylnaltrexone, a subcutaneously administered peripherally acting mu opioid receptor antAgonist, has recently been approved for opioid-induced constipation in terminally ill patients. New agents under evaluation include the 5-HT4 Agonists velusetrag and naronapride, the guanylate cyclase-C receptor Agonist linaclotide and the peripherally acting mu opioid receptor antAgonist alvimopan.

Bernard Soumireu-mourat – 3rd expert on this subject based on the ideXlab platform

  • Differential modulation of the 5-HT4 receptor Agonists and antAgonist on rat learning and memory
    Neuropharmacology, 2000
    Co-Authors: Evelyne Marchetti, Aline Dumuis, Joel Bockaert, Bernard Soumireu-mourat, Francois Roman

    Abstract:

    Abstract Recent data suggest that activation of 5-HT4 receptors may modulate cognitive processes such as learning and memory. In the present study, the effects of two potent and selective 5-HT4 Agonists, RS 17017 [1-(4-amino-5-chloro-2-methoxyphenyl)-5-(piperidin-1-yl)-1-pentanone hydrochloride] and RS 67333 [1(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone], were studied in an olfactory associative discrimination task. The implication of 5-HT4 receptors in the associative discriminative task was suggested by the following observation. Injection of a selective 5-HT4 receptor antAgonist RS 67532 [1-(4-amino-5-chloro-2-(3,5-dimethoxybenzyloxyphenyl)-5-(1-piperidinyl)-1-pentanone; 1 mg/kg: i.p.] before the third training session induced a consistent deficit in associative memory during the following training sessions. This deficit was absent when the antAgonist was injected together with either a specific hydrophilic 5-HT4 (RS 17017, 1 mg/kg) or a specific hydrophobic (RS 67333, 1 mg/kg) 5-HT4 receptor Agonist. RS 67333 was more potent than RS 17017. This difference in potency certainly reflects a difference in their capacity to enter into the brain. This is also likely to be the reason why, injected alone, the hydrophobic 5-HT4 Agonist (RS 67333) but not the hydrophilic 5-HT4 Agonist (RS 17017) improved learning and memory performance.

  • BIMU1 increases associative memory in rats by activating 5-HT4 receptors.
    Neuropharmacology, 1997
    Co-Authors: E Marchetti-gauthier, Aline Dumuis, Joel Bockaert, F S Roman, Bernard Soumireu-mourat

    Abstract:

    Olfactory association learning was used to investigate the involvement of 5-HT4 receptors in learning and long-term memory. The behavioral role of the 5-HT4 receptors was studied by using BIMU1 (3-ethyl-2,3-dihydro-N-[endo-8-methyl-8-azabicyclo(3.2.1)oct-3-yl]-2-oxo -1 H-benzimidazole-1-carboxamide, hydrochloride (Boehringer Ingelheim, Italy); a mixed 5-HT4 Agonist/5-HT3 antAgonist, and GR125487 (1-[2-[methyl sulphonyl)-amino]ethyl]-4-piperidinyl-methyl 5-fluro-2-methoxy-1H-indole-3- carboxylate; Glaxo Group Research, Hertfordshire, U.K.), a specific 5-HT4 antAgonist. The intraperitoneal injections of BIMU1 at 1, 5, and 10 mg/kg were followed by an substantial improvement (> 15% in percentage of correct responses at the dose of 10 mg/kg) in associative memory. Difficulty rapidly reversing behavioral responses to previously learned association, 1 month later indicated that the BIMU1 effect at 10 mg/kg was not transient, but correlated to long-term memory. The effects of BIMU1 are most likely to be mediated by 5-HT4 receptors since they were blocked by GR125487 at 10 mg/kg. These data suggest that activation of 5-HT4 receptors may modulate cognitive processes like learning and memory.

  • BIMU1 Increases Associative Memory in Rats by Activating 5-HT4 Receptors
    Neuropharmacology, 1997
    Co-Authors: E Marchetti-gauthier, Francois Roman, Aline Dumuis, Joel Bockaert, Bernard Soumireu-mourat

    Abstract:

    Abstract Olfactory association learning was used to investigate the involvement of 5-HT4 receptors in learning and long-term memory. The behavioral role of the 5-HT4 receptors was studied by using BIMU1 (3-ethyl-2,3-dihydro-N-[endo-8-methyl-8-azabicyclo(3.2.1)oct-3-yl]-2-oxo-1H-benzimidazole-1-carboxamide, hydrochloride (Boehringer Ingelheim, Italy); a mixed 5-HT4 Agonist/5-HT3 antAgonist, and GR125487 (1-[2-[methyl sulphonyl)-amino]ethyl]-4-piperidinyl-methyl 5-fluoro-2-methoxy-1H-indole-3-carboxylate; Glaxo Group Research, Hertfordshire, U.K.), a specific 5-HT4 antAgonist. The intraperitoneal injections of BIMU1 at 1, 5, and 10 mg/kg were followed by an substantial improvement (>15% in percentage of correct responses at the dose of 10 mg/kg) in associative memory. Difficulty rapidly reversing behavioral responses to previously learned association, 1 month later indicated that the BIMU1 effect at 10 mg/kg was not transient, but correlated to long-term memory. The effects of BIMU1 are most likely to be mediated by 5-HT4 receptors since they were blocked by GR125487 at 10 mg/kg. These data suggest that activation of 5-HT4 receptors may modulate cognitive processes like learning and memory. © 1997 Elsevier Science Ltd.