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                <term xml:lang="en">gastrointestinal disorders</term>
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                <term xml:lang="en">Alzheimer</term>
                <term xml:lang="en">central nervous system</term>
                <term xml:lang="en">depression</term>
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              <p>Introduction: Numerous chemotypes have been described over time in order to generate potent and selective 5-HT4R ligands. Both agonists and antagonists have demonstrated their interest in several disease models. This culminates with the FDA approval of tegaserod and prucalopride in the recent years.Areas covered: This review summarizes the patent applications from 2014 to present, dedicated to the use or the description of novel 5-HT4R modulators. Several novel ligands and scaffolds have been industrially protected mainly in the field of central nervous system (CNS) pathologies as well as gastrointestinal disorders, including the combination with other drugs or for veterinary uses.Expert opinion: The therapeutic potential of 5-HT4R modulators has been explored for several years in animal models, but also linked to potential safety issues with initial ligands. The current use of prucalopride in humans demonstrates that its toxicity is not linked to the target and that 5-HT4R modulators are safe in humans. Therefore, an important number of studies and patents has continued in the recent years to expand the use of 5-HT4R modulators, not only to treat gastrointestinal disorders, but also for CNS pathologies. This article details current efforts in this development.</p>
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