GI hypomotility

• Achalasia of the esophagus
• Gastroparesis
• Chronic intestinal dysmotility
• Ileus
• Gastroesophageal reflux disease

Stimulate gastric emptying

Accelerate small and large intestinal transit

1. Myenteric Plexus
2. Submucosal Plexus

• Prokinetic action is not completely understood
• D2 receptor antagonist, which crosses the BBB
• Believed to facilitate ACh release from the excitatory motor neuron
• Its effects can be antagonized by atropine
• May sensitize muscarinic receptors
• Is also a weak 5HT-3 receptor antagonist (has nothing to do with its prokinetic action)

• Enhances propulsive activity in a coordinated manner, leading to increased tone and motility in the esophagus and stomach
• Accelerates gastric emptying by preventing relaxation of the gastric body and increasing phasic contractions of the antrum
• Increases the resting pressure of the lower esophageal sphincter and reduces reflux of acid

Hyperprolactinemia

CNS D2 blockade (tardive dyskinesia, pseudoparkinsoniasm, akathesia, torticollis)

• Partial agonist at 5HT-4 receptors located in the primary afferent and nerve terminal of motor neuron in the myenteric plexus
• 5HT-4 agonists stimulate ACh release from myenteric motor neurons
• Enhances peristalsis in the small intestine
• Enhances gastric emptying

• Mimics the effects of the GI polypeptide motilin
• Increases smooth muscle contractility, especially upper GI 
• Enhances gastric emptying, Increases antral contractions, and increases antroduodenal coordination
• Has little effect on colonic motility
• Results in "Dumping Syndrome"

• A hormone release from endocrine cells (M cells) in the duodenal mucosal layer
• Increases motility during interdigestive periods
• Motilin receptors are found mainly in the smooth muscle cells and nerve endings -- they are GPCRs that link to the activation of Gq and G13, resulting in phosphoinositide hydrolysis

Peripherally acting μ-receptor antagonist (does not cross BBB)