Serotonergic mediation of vomiting

Area of Science:

• Neuroscience
• Pharmacology
• Gastroenterology

Background:

• The emetic reflex, particularly chemotherapy-induced nausea and vomiting (CINV), has seen significant advancements in understanding and treatment.
• 5-hydroxy-tryptamine (5-HT, serotonin) has been identified as crucial in the pathogenesis of emesis.

Purpose of the Study:

• To review the role of serotonin in the emetic reflex.
• To discuss the efficacy of 5-HT3 receptor antagonists in managing chemotherapy- and radiotherapy-induced emesis.
• To explore potential alternative therapeutic targets for nausea and vomiting.

Main Methods:

• Review of pharmacologic and physiologic investigations in animals and humans.
• Analysis of clinical data on the efficacy of 5-HT3 receptor antagonists.
• Examination of the role of different serotonin receptor subtypes in emesis.

Main Results:

• Serotonin (5-HT) is released by chemotherapeutic and radiation agents from intestinal enterochromaffin cells and possibly brainstem neurons.
• Stimulation of 5-HT3 receptors centrally and peripherally is pivotal in eliciting emesis.
• 5-HT3 receptor antagonists like ondansetron and granisetron are effective in treating cancer treatment-related emesis.

Conclusions:

• Serotonin (5-HT) plays a fundamental role in the emetic reflex, especially in the context of cancer therapies.
• Targeting 5-HT3 receptors is a successful strategy for managing severe nausea and vomiting.
• Interactions with other serotonin receptors (e.g., 5-HT1A, 5-HT4) may offer future therapeutic avenues for emesis treatment.