In a healthy human esophagus, swallowing induces primary peristalsis. This begins the process of moving food through the digestive tract. In turn, gastroesophageal reflux provokes a second wave of muscular contractions that clears the esophagus, pushing food down through the lower esophageal sphincter (LES) and into the stomach.

However, in some people, the LES either relaxes or opens spontaneously, allowing stomach contents—including acids—to re-enter the esophagus. This is called acid reflux and may lead to symptoms like heartburn.

Prokinetic agents, or prokinetics, are medications that help control acid reflux. Prokinetics help strengthen the lower esophageal sphincter (LES) and cause the contents of the stomach to empty faster. This allows less time for acid reflux to occur.

Today, prokinetics are typically used with other gastroesophageal reflux disease (GERD) or heartburn medications, such as proton pump inhibitors (PPIs) or H2 receptor blockers. Unlike these other acid reflux medications, which all generally are safe, prokinetics may have serious or even dangerous side effects. They’re often only used in the most serious cases of GERD.

For example, prokinetics might be used to treat patients who also have insulin-dependent diabetes, or infants and children with significantly impaired bowel emptying or severe constipation that doesn’t respond to other treatments.  

Types of Prokinetics

Bethanechol

Bethanechol (brand name: Urecholine) is a parasympathomimetic choline carbamate available in tablet form. It helps to strengthen the LES and make the stomach empty faster. It also helps prevent nausea and vomiting.

However, its usefulness may be outweighed by frequent side effects. Side effects can include anxiety, depression, drowsiness, fatigue, and physical problems such as involuntary movements and muscle spasms.  

Cisapride

Cisapride (brand names: Prepulsid and Propulsid) was discovered by Janssen Pharmaceutica in 1980. Cisapride acts on serotonin receptors in the stomach and was primarily used to improve muscle tone in the LES.

Cisapride was once considered as effective in treating GERD as H2 receptor blockers such as famotidine (Pepcid, Pepcid AC) and ranitidine (Zantac). However, due to side effects such as irregular heartbeat, it has been removed from the market in several countries, including the United States. Cisapride is still often used in veterinary medicine.

Domperidone

The prokinetic agent domperidone (brand names: Costi, Motilium, Motillium, and Motinorm), like cisapride, was developed by Janssen Pharmaceutica. Also like cisapride, it is unavailable in the United States. However, it’s still used in several other countries as treatment for acid reflux and GERD—especially in newborns and infants.

A 2009 study published in the Journal of Perinatology found that domperidone had "little effect on the central nervous system" of newborns. This makes it safer to use in children than other prokinetics. However, researchers concluded that, because of the adverse effects of other drugs, the effectiveness of domperidone in this age group is doubtful.

Metoclopramide

Metoclopramide (brand name: Reglan) is a prokinetic agent that has been used to treat GERD by improving muscle action in the gastrointestinal tract. It’s available in both tablet and liquid forms. Like other prokinetics, metoclopramide's efficacy is hindered by serious side effects.

Side effects may include an increased risk of neurological conditions, such as tardive dyskinesia in patients who remain on the drug for more than three months. People taking metoclopramide also should be extremely cautious while driving or operating heavy machinery or equipment.