Prokinetic agents (prokinetics) are medications that help control acid reflux in severe cases of gastroesophageal reflux disease (GERD). They help strengthen the lower esophageal sphincter (LES) and cause the contents of the stomach to empty faster.

The word “prokinetic” refers to the act of encouraging movement. Prokinetic agents can be helpful in treating conditions that cause dysmotility, which is when the stomach isn’t able to properly pass food.

Read on to learn about how prokinetics are used for GERD, the various types, as well as their benefits and side effects.

In a healthy human esophagus, swallowing induces primary peristalsis. These are the contractions that move your food down your esophagus and through the rest of your digestive system.

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 reenter the esophagus. This is called acid reflux and may lead to symptoms like heartburn.

Today, prokinetics are typically used with other gastroesophageal reflux disease (GERD) or heartburn medications, such as proton pump inhibitors (PPIs), antacids, or H2 receptor blockers.

Prokinetics are typically reserved for severe cases of GERD and other digestive conditions, such as gastroparesis or dyspepsia, as many of them are associated with significant side effects.

For example, prokinetics might be used to treat people 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.

Prokinetics can be classified into several sub-types:

  • Cholinergic agonists: These affect cetylcholine, the main neurotransmitter in the parasympathetic nervous system (PNS), which controls digestion. They can be direct-acting and indirect-acting. They include medications such as Bethanechol (Urecholine) or cevimeline (Evoxac).
  • Dopamine antagonists: These work by attaching to and obstructing the neurotransmitter dopamine receptors. An example of a dopamine antagonist used to treat GERD by improving muscle action in the gastrointestinal tract is Metoclopramide (Reglan, Metozolv ODT).
  • Macrolides: These are antibiotics with a prokinetic effect. They include azithromycin (Zithromax) and erythromycin (Ery-tab). The latter is more commonly used to treat reflux in children.
  • Serotonergic agonists: These work by activating the neurotransmitter serotonin. Tegaserod (Zelnorm) is an example of such a drug used to treat GERD and irritable bowel syndrome (IBS) symptoms.

According to a 2019 study examining 309 people treated with prokinetics, more than half (59%) experienced at least one side effect.

Every prokinetic agent will have different side effects, though there is some overlap. Generally, they can cause things like abdominal cramping, vomiting, diarrhea, or physical problems such as involuntary movements and muscle spasms.

Some specific drugs are known for particularly serious risks:

Cisapride (Janssen-Ortho, Propulsid)

Cisapride (Propulsid) acts on serotonin receptors in the stomach. It was primarily used to improve muscle tone in the LES and was considered as effective in treating GERD as H2 receptor blockers such as famotidine (Pepcid) can be.

Because of its side effects, such as irregular heartbeat, it has been removed from the market in several countries, including the United States.

However, it’s still often used in veterinary medicine.

Metoclopramide (Reglan, Metozolv ODT)

Metoclopramide is still available in the U.S. in tablet and liquid forms. However, its efficacy is hindered by serious side effects.

These may include:

  • higher chance of tardive dyskinesia
  • depression
  • neuroleptic malignant syndrome
  • parkinsonism
  • hyperprolactinemia

These side effects have been known to occur in people who remain on the drug for more than three months. People taking metoclopramide should be extremely cautious while driving or operating heavy machinery or equipment.

All prokinetic agents are associated with some degree of side effects, and only your doctor can tell you if, for you, the benefits might outweigh the risks.

That said, according to a 2023 study on the treatment of dyspepsia, researchers found that metoclopramide and cinitapride (Cintapro, Pemix) were a bit more effective than other prokinetics. They also found that cinitapride may be associated with fewer side effects. However, cinitapride isn’t available in the United States.

Learn more: How to tell whether gastroesophageal reflux disease (GERD) is under control.

While no research supports the idea that any natural substances are as effective as prokinetic agents, there are some herbs that may help reduce symptoms of dyspepsia, acid reflux, or GERD. These include:

Speak with your doctor first if you are considering combining these with any of your medications to make sure there would be no negative interactions.

Learn more: Is it possible to cure gastroesophageal reflux disease (GERD)?

Prokinetic agents, often known as prokinetics, are drugs that help reduce acid reflux in severe cases of GERD and other conditions related to digestion.

They work by speeding up the emptying of the stomach by strengthening the LES. However, many of these drugs come with side effects, some of which can be dangerous.

Work with your doctor to figure out which treatment plan is right for you and whether a prokinetic agent is a good choice. Make sure you follow the directions your doctor gives you. Call your doctor if you feel like your medications have caused negative side effects.