Domperidone: mechanism of action and clinical applications in gastroenterology

General Description

Domperidone is a dopamine receptor antagonist used to treat gastrointestinal diseases. It blocks dopamine's action on the Dop2 receptor, regulating gastrointestinal motility and alleviating symptoms such as nausea, vomiting, and abdominal pain. Domperidone is commonly used for conditions like gastroesophageal reflux disease (GERD), dyspepsia, and postoperative nausea and vomiting. Its effectiveness in treating GERD is uncertain compared to proton pump inhibitors (PPIs), but it may complement PPI therapy in specific cases. It has shown promising results in relieving symptoms of chronic dyspepsia. Domperidone has antiemetic properties and can manage postoperative nausea and vomiting as well as chemotherapy-induced nausea and vomiting, although strongly emetic drugs may be more challenging to control.

Figure 1. Capsules of domperidone

Mechanism of action

Domperidone is a dopamine receptor antagonist that is primarily used to treat gastrointestinal diseases. It works by blocking the action of dopamine on the Dop2 receptor in the enteric nervous system, which helps to regulate gastrointestinal motility. This in turn can help to alleviate symptoms associated with gastrointestinal diseases such as nausea, vomiting, and abdominal pain. Additionally, domperidone has been shown to increase the release of prolactin, which may have beneficial effects on gastrointestinal function. In particular, domperidone is often used to treat GERD, which is a condition characterized by acid reflux and heartburn. By blocking the Dop2 receptor, domperidone helps to reduce the frequency and severity of GERD symptoms, including heartburn, regurgitation, and chest pain. It can also be used to treat other gastrointestinal diseases such as irritable bowel syndrome (IBS) and constipation. It is important to note that domperidone is not indicated for use in pregnant or breastfeeding patients and should be used with caution in patients with heart disease or arrhythmias. In conclusion, domperidone treats gastrointestinal diseases by blocking the action of dopamine on the Dop2 receptor in the enteric nervous system, which helps to regulate gastrointestinal motility. ¹

Clinical applications in gastroenterology

Gastroesophageal feflux disease

In short, the effectiveness of domperidone in reducing reflux severity and symptoms of GERD has shown mixed results in previous trials. It was found to be no more effective than placebo in one study, while another study demonstrated that it was equally as effective as ranitidine in symptom reduction and promoting esophagitis healing. However, these trials were conducted before the widespread use of proton pump inhibitors (PPIs), which are considered more effective for controlling heartburn. Domperidone may have a role as a complementary therapy with PPIs, especially in cases where there is delayed gastric emptying or after fundoplication surgery. ²

Dyspepsia

Dyspepsia symptoms include postprandial fullness, epigastric pain, burning, early satiety, and nausea. A study with over 200 patients found that 78% of individuals benefited significantly from a daily dose of 30-60 mg of domperidone for chronic dyspepsia. Another study with 41 patients showed that a daily dose of 30 mg of oral domperidone effectively reduced postprandial distress associated with chronic dyspepsia. Overall, these studies suggest that domperidone can provide symptomatic relief for chronic dyspepsia. ³

Nausea and Vomiting

Domperidone is well-documented for its antiemetic properties. In postoperative patients, intravenous domperidone has shown greater effectiveness than a placebo in managing nausea and vomiting. However, neither domperidone nor metoclopramide has proven to be more effective than a placebo when used prophylactically before anesthesia induction or near the end of anesthesia. When it comes to nausea and vomiting associated with cytotoxic drug therapy, domperidone has been successful in controlling these symptoms when administered prior to the cytotoxic treatment. It has demonstrated superiority over a placebo and comparable results to metoclopramide in managing vomiting caused by moderately emetic cytotoxic drugs. It should be noted that strongly emetic drugs like mustine and dacarbazine pose more challenging control of nausea and vomiting. Overall, domperidone can be effective in managing postoperative nausea and vomiting as well as nausea and vomiting induced by cytotoxic drugs, with varying degrees of success depending on the specific circumstances and types of medication involved. ⁴

Reference

1. Nishimae F, Sakurai F, Ono R, Onishi R, Takayama K, Mizuguchi H. A dopamine antagonist, domperidone enhances the replication of an oncolytic adenovirus in human tumour cells. J Gen Virol, 2022, 103(6).

2. Maddern GJ, Kiroff GK, Leppard PI, et al. Domperidone, metoclopramide, and placebo. All give symptomatic improvement in gastroesophageal reflux. J Clin Gastroenterol, 1986, 8:135–140.

3. Milo R. Use of the peripheral dopamine antagonist, domperidone, in the management of gastro-intestinal symptoms in patients with irritable bowel syndrome. Curr Med Res Opin, 1980, 6:577–584.

4. Hamers J. Cytostatic therapy-induced vomiting inhibited by domperidone. A double-blind cross-over study. Biomedicine, 1978, 29:242–244.