Serotonergic modulating drugs for functional gastrointestinal diseases

Area of Science:

• Gastroenterology
• Neurogastroenterology
• Pharmacology

Background:

• Basic research has elucidated the manipulation of gut serotonergic mechanisms.
• Serotonin (5HT) pathways in the gut are increasingly understood and targeted therapeutically.

Purpose of the Study:

• To review advances in manipulating gut serotonergic mechanisms for functional gastrointestinal disorders.
• To discuss the therapeutic potential and limitations of targeting various serotonin receptors (5HT3, 5HT4, 5HT1) in the gut.
• To consider the role of anxiety in functional gut symptoms and the potential for centrally acting agents.

Main Methods:

• Review of current literature on serotonergic agents in gastroenterology.
• Analysis of clinical applications and adverse events of 5HT receptor modulators.
• Discussion of the interplay between peripheral and central nervous system effects.

Main Results:

• 5HT3 antagonists are used for functional diarrhea.
• 5HT4 agonists are effective for constipation.
• 5HT1 agonists aid in impaired fundal relaxation.
• Alosetron (a 5HT3 antagonist) withdrawal due to ischemic colitis highlights safety concerns.
• Anxiety is a significant comorbidity in functional gut disorders.

Conclusions:

• Targeting gut serotonin receptors has yielded significant therapeutic advances for functional gastrointestinal disorders.
• Safety profiles, such as ischemic colitis with 5HT3 antagonists, require careful monitoring.
• The high prevalence of anxiety suggests a need for treatments with combined peripheral and central nervous system effects.