5‐HT4 receptor agonists: similar but not the same

  title={5‐HT4 receptor agonists: similar but not the same},
  author={Joris H. De Maeyer and Romain Adelin Lefebvre and J. A. J. Schuurkes},
  journal={Neurogastroenterology \& Motility},
Abstract  5‐Hydroxytryptamine4 (5‐HT4) receptors are an interesting target for the management of patients in need of gastrointestinal (GI) promotility treatment. They have proven therapeutic potential to treat patients with GI motility disorders. Lack of selectivity for the 5‐HT4 receptor has limited the clinical success of the agonists used until now. For instance, next to their affinity for 5‐HT4 receptors, both cisapride and tegaserod have appreciable affinity for other receptors, channels… 

Translating 5‐HT4 receptor pharmacology

  • G. Sanger
  • Biology
    Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society
  • 2009
The progress of this compound for treatment of chronic constipation, as well as competitor molecules such as ATI‐7505 and TD‐5108, will now be followed with interest as each attempts to differentiate themselves from each other.

The in vitro pharmacology and non‐clinical cardiovascular safety studies of a novel 5‐HT4 receptor agonist, DSP‐6952

Pulmonary , gastrointestinal and urogenital pharmacology Pharmacological pro fi le of DA-6886 , a novel 5-HT 4 receptor agonist to accelerate colonic motor activity in mice

DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation.

New-generation 5-HT4 receptor agonists: potential for treatment of gastrointestinal motility disorders

Prucalopride, ATI-7505, and velusetrag are highly selective, high-affinity 5-HT4 receptor agonists that are devoid of action on other receptors within their therapeutic range that are promising approaches to treat GI dysmotility, particularly colonic diseases.

5-hydroxytryptamine and the gastrointestinal tract: where next?

  • G. Sanger
  • Biology
    Trends in pharmacological sciences
  • 2008

Role of prucalopride, a serotonin (5-HT4) receptor agonist, for the treatment of chronic constipation

Prucalopride is a well tolerated and efficacious prokinetic medication that should enhance the treatment of chronic constipation unresponsive to first-line treatments.

The Pharmacology of TD-8954, a Potent and Selective 5-HT4 Receptor Agonist with Gastrointestinal Prokinetic Properties

It is concluded that TD-8954 is a potent and selective 5-HT4 receptor agonist in vitro, with robust in vivo stimulatory activity in the gastrointestinal (GI) tract of guinea pigs, rats, dogs, and humans and may have clinical utility in patients with disorders of reduced GI motility.



The 5‐HT4 receptor agonist, tegaserod, is a potent 5‐HT2B receptor antagonist in vitro and in vivo

The data from this study indicate that tegaserod antagonizes 5‐ HT2B receptors at concentrations similar to those that activate 5‐HT4 receptors.

Review article: 5‐hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical implications

  • N. J. Talley
  • Biology
    Alimentary pharmacology & therapeutics
  • 1992
It has been suggested that specific 5‐HT antagonists and agonists may prove to be beneficial in a number of gastrointestinal disorders including the irritable bowel syndrome, functional dyspepsia, non‐cardiac chest pain, gastrooesophageal reflux and refractory nausea.

Characterization of human 5‐HT4(d) receptor desensitization in CHO cells

It is demonstrated that the C‐terminal tail of h5‐HT4 receptors may influence the rate of agonist‐induced desensitization and there is evidence for a major role of PKA in h5-HT4(d) receptor desensItization.

Interactions of metoclopramide and ergotamine with human 5‐HT3A receptors and human 5‐HT reuptake carriers

The actions of metoclopramide and ergotamine, drugs which are used as a combined migraine medication, on human (h)5‐HT3A receptors and 5‐HT reuptake carriers, were studied with patch‐clamp‐ and ([3H]5‐ HT)‐uptake techniques.

The serotonin 5-HT4 receptor. 2. Structure-activity studies of the indole carbazimidamide class of agonists.

A number of substituted indole carbazimidamides were prepared and evaluated as 5-HT4 receptor agonists by using the isolated field-stimulated guinea pig ileum preparation and several selective and highly potent full as well as partial agonists emerged.

Tegaserod‐Induced Myocardial Infarction: Case Report and Hypothesis

The first case of a man who experienced a myocardial infarction after receiving only two 6‐mg doses of tegaserod is reported, and a hypothesis regarding this event is provided.

Characterization of the 5‐HT4 receptor mediating tachycardia in piglet isolated right atrium

The sinoatrial 5‐ HT4 receptor in the piglet has a pharmacological profile that correlates well with 5‐HT4 receptors characterized in rat oesophagus, guinea‐pig ileum and colon, mouse embryonic colliculi neurones and human atrium.

5-HT4 Receptors

The similarities between the molecular mechanisms of action of 5-HT4 receptors and those in Aplysia (sea hare) neurons may suggest a role for the receptors in synaptic plasticity events and memory processes.

Drugs Acting on Serotonin Receptors for the Treatment of Functional GI Disorders

The role of non-neuronal (paracrine) and neuronal 5-HT in the pathophysiology of functional gastrointestinal disorders (FGIDs), such as IBS and functional dyspepsia, and the mechanisms through which drugs acting on 5- HT receptors regulate visceral motility, perception and secretion in these two conditions are discussed.

5-HT(4) receptor antagonists: structure-affinity relationships and ligand-receptor interactions.

This article will review the development of the most important classes of 5-HT(4R) antagonists with an emphasis on benzimidazole derivatives, their structure-affinity relationships, ligand-receptor interactions and pharmacological applications.