Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food transit.

Metoclopramide (Primperan) enhances GI motility, both by blocking dopamine receptors and increasing the release of acetylcholine, another neurotransmitter that promotes GI motility. It is absorbed quickly and acts within 1-2 hours of oral intake. It has a half-life of 4-6 hours. It undergoes hepatic sulfation and glucuronide conjugation and is excreted in the urine. It treats gastroparesis, gastroesophageal reflux disease (GERD), and nausea/vomiting but can lead to side effects like extrapyramidal symptoms, dystonias, dyskinesias, sedation, and hyperprolactinemia.

Domperidone (Motilium) also increases GI motility by blocking dopamine receptors but has fewer central nervous system side effects than metoclopramide. However, it may increase the risk of cardiac arrhythmias. It is metabolized by hepatic CYP3A4, N-dealkylation, and hydroxylation pathways. It is primarily used to treat nausea and vomiting. Notably, it is available through expanded access to investigational drugs with the FDA.