Serotonergic Signaling in Gastric Physiology and Motility Disorders

Area of Science:

• Gastroenterology and Neuropharmacology: Focus on the role of serotonin in the gastrointestinal tract.

Background:

• Serotonin (5-hydroxytryptamine; 5-HT) is a key regulator of gastrointestinal function, released by enterochromaffin cells.
• Altered serotonergic signaling contributes to gastric motility disorders, making it a significant therapeutic target.
• Previous agents like cisapride were withdrawn; newer, receptor-specific ligands offer a revised therapeutic landscape.

Purpose of the Study:

• To synthesize current knowledge on serotonergic pathways in gastric physiology and motility disorders.
• To clarify therapeutic applications of serotonergic agents in conditions such as gastroparesis (GP) and functional dyspepsia (FD).
• To identify remaining evidence gaps in the use of serotonergic therapies.

Main Methods:

• Review integrates molecular, physiological, and clinical data on serotonin's role in the gut.
• Analysis of current guidelines and evidence for specific serotonergic agents (5-HT4 agonists, 5-HT3 antagonists, etc.).
• Examination of emerging agents and their potential benefits and risks.

Main Results:

• 5-HT4 agonists are recommended for gastroparesis (GP) management, improving gastric emptying and symptoms.
• 5-HT3 antagonists are used for nausea and vomiting control.
• Selective use of 5-HT2 antagonists (mirtazapine) and 5-HT1A agonists (buspirone) considered for functional dyspepsia (FD) based on symptoms.

Conclusions:

• Serotonergic modulation remains relevant for gastric motility disorders, with newer agents like naronapride showing promise.
• While 5-HT4 agonists and 5-HT3 antagonists have established roles, further research is needed for SSRIs/SNRIs.
• Large controlled trials are lacking, highlighting the need for continued investigation into serotonergic therapies for GP and FD.