Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

Serotonin, also known as 5-Hydroxytryptamine or 5-HT, is a neurotransmitter crucial for regulating gut motility.

Within the GI tract, enterochromaffin cells respond to chemical or mechanical stimuli by releasing serotonin, which stimulates myenteric plexus, vagal, and spinal sensory neurons. This initiates peristalsis, a coordinated contraction process for moving food through the GI tract.

Furthermore, serotonin stimulates 5-HT₄ receptors on excitatory motor neurons, increasing acetylcholine levels at the neuromuscular junction. This stimulates motility across the stomach, small intestine, and colon with specific peristaltic contractions in the proximal colon, propelling fecal contents.

Using 5-HT₄ agonists, such as prucalopride and cisapride, can help treat GI dysmotility.

Although cisapride is a rapidly acting agonist, it induces fatal cardiac arrhythmias.

Prucalopride, more selective, enhances colonic contractions, relieving chronic constipation but may cause side effects such as nausea, abdominal pain, diarrhea, and headaches.