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5-HT4 receptors.

J Bockaert1, S Claeysen, V Compan

  • 1UPR CNRS 2580-CCIPE, 141 rue de la Cardonille, 34094 Montpellier cedex 5, France. joel.bockaert@ccipe.cnrs.fr

Current Drug Targets. CNS and Neurological Disorders
|February 18, 2004
PubMed
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Serotonin 4 receptors (5-HT4Rs) exhibit complex gene expression with multiple variants. Research suggests these receptors are potential therapeutic targets for cognitive deficits and other disorders.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • Serotonin 4 receptors (5-HT4Rs) are a class of G protein-coupled receptors involved in various physiological processes.
  • The gene encoding 5-HT4Rs is complex, spanning 700Kb with 38 exons, leading to the generation of at least eight distinct carboxy-terminal variants (a-g, n).
  • Sequence variations occur after amino acid position L358, and one variant features a 14-residue insertion in extracellular loop 2.

Purpose of the Study:

  • To review the current understanding of serotonin 4 receptors (5-HT4Rs), including their genetic complexity and functional implications.
  • To highlight the potential of 5-HT4Rs as therapeutic targets for neurological and gastrointestinal disorders.
  • To identify the need for specific pharmacological tools, particularly full agonists, for further research.

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Main Methods:

  • Review of existing literature on serotonin 4 receptor (5-HT4R) genetics, pharmacology, and physiology.
  • Analysis of reported sequence variations and receptor variants.
  • Examination of data from physiological and behavioral experiments investigating 5-HT4R roles.

Main Results:

  • The serotonin 4 receptor (5-HT4R) gene is highly complex, yielding multiple protein variants with differing sequences.
  • Selective antagonists and partial agonists for 5-HT4Rs that penetrate the blood-brain barrier have been developed.
  • A specific full agonist for brain studies remains unavailable.

Conclusions:

  • Serotonin 4 receptors (5-HT4Rs) present a promising target for therapeutic interventions.
  • Potential applications include the treatment of cognitive deficits, memory impairment, dementia, abdominal pain, and feeding disorders.
  • Ongoing research and development of specific pharmacological agents, like the drug SL65.0155 in Phase II trials, are crucial for realizing the therapeutic potential of 5-HT4Rs.