What is the mechanism of Domperidone?

Domperidone is a medication primarily used to treat nausea and vomiting, as well as to facilitate gastric motility disorders. Understanding the mechanism of domperidone involves a closer look at its pharmacological actions, its effects on the body, and its therapeutic applications.

Domperidone is a peripherally selective dopamine D2 and D3 receptor antagonist. It does not cross the blood-brain barrier significantly, which distinguishes it from other dopamine antagonists that have central nervous system effects. This selective action is crucial because it allows domperidone to exert its effects predominantly in the gastrointestinal tract rather than the brain.

The primary mechanism of domperidone involves its antagonistic action on dopamine receptors located in the chemoreceptor trigger zone (CTZ) and the gastrointestinal tract. By blocking dopamine D2 and D3 receptors in the CTZ, domperidone helps to alleviate nausea and vomiting. Dopamine is a neurotransmitter that can induce emesis (vomiting) when it acts on these receptors. By inhibiting this action, domperidone effectively reduces the sensation of nausea and the occurrence of vomiting.

In addition to its antiemetic properties, domperidone's blockade of dopamine receptors in the gastrointestinal tract enhances gastric motility. Dopamine normally inhibits gastrointestinal motility by relaxing the smooth muscles and reducing peristalsis. By antagonizing dopamine receptors, domperidone promotes the contraction of the smooth muscles and increases peristalsis, thus facilitating the movement of food through the stomach and intestines. This prokinetic effect is particularly beneficial in conditions such as gastroparesis, where delayed gastric emptying causes symptoms like bloating, early satiety, and discomfort.

Furthermore, domperidone increases the tone of the lower esophageal sphincter (LES). This action helps to prevent gastroesophageal reflux, a condition where stomach acid flows back into the esophagus, causing heartburn and potential damage to the esophageal lining. By strengthening the LES, domperidone helps to keep stomach contents from refluxing back up into the esophagus.

Domperidone also has an effect on prolactin levels due to its dopamine-blocking properties. Dopamine inhibits the release of prolactin from the pituitary gland, so by blocking dopamine receptors, domperidone can increase the levels of prolactin. Elevated prolactin levels can stimulate lactation (milk production) in breastfeeding mothers, which is sometimes a desired therapeutic effect.

In summary, the mechanism of domperidone is primarily based on its ability to block dopamine D2 and D3 receptors in the chemoreceptor trigger zone and the gastrointestinal tract. This action reduces nausea and vomiting, enhances gastric motility, increases the tone of the lower esophageal sphincter, and affects prolactin levels. These combined effects make domperidone a versatile medication in the management of various gastrointestinal disorders and conditions associated with nausea and vomiting.