What to Know About Prokinetic Agents

Medically Reviewed by Minesh Khatri, MD on September 14, 2023
3 min read

Prokinetic is a term that means to promote movement. Some conditions that affect the muscles and nerves of your gastrointestinal (GI) tract can cause you to have dysmotility. Dysmotility is when your GI tract doesn't move food through your digestive system the way it should. Prokinetic agents are medicines that help stimulate your gastrointestinal tract to help this process.

As soon as you start eating, your body begins the process of digesting your food. It does this through peristalsis. Peristalsis is a series of wave-like contractions that moves your food from your esophagus to your stomach and small intestines. These contractions help your body absorb nutrients from your food. Peristalsis is also an important part of moving your food to your rectum where it can be excreted as waste.

You have nerves and muscles that are involved in peristalsis. Disorders that interfere with how these nerves and muscles work can cause issues with this function. Sometimes the problem can be in your lower esophageal sphincter (LES), a bundle of muscles at the bottom of your esophagus. When your LES is closed, it prevents the contents of your stomach from going back up into your esophagus. 

If your LES isn't working properly, you may experience acid reflux or heartburn. Prokinetic agents strengthen the contractions of your LES muscles and help stimulate the other muscle contractions in the entire GI tract.  

There are several types of prokinetic agents, including:

Cholinergic agonists. These medications act on the neurotransmitter acetylcholine, which is part of your parasympathetic nervous system (PNS).  Neurotransmitters carry messages throughout nerve cells. One of the functions of the PNS is controlling your digestion. The prokinetic agents in this class include bethanechol, which was used to treat heartburn and gastroparesis, a condition that causes partial paralysis in your stomach.

Bethanechol is not often used for this anymore because of its side effects. Neostigmine and pyridostigmine are two other cholinergic agonists that are still used for certain conditions that slow down peristalsis, such as Ogilvie's syndrome and pseudo-obstruction.  

Dopamine antagonists. Metoclopramide and domperidone are two types of prokinetic dopamine antagonists. These work by binding with and blocking dopamine receptors, which is a type of neurotransmitter. Metoclopramide, which was sold under the brand name Reglan, is used to treat gastroparesis and heartburn.

Domperidone is not approved for use in the US without special permission from the FDA. There are serious risks associated with domperidone, including abnormal heart rhythms, heart attack, and even sudden death.

Serotonergic agonists. Serotonergic agonists work by activating serotonin receptors, which is another type of neurotransmitter. Cisapride, prucalopride, and tegaserod are examples of medicines that work this way. Unfortunately, cisapride and tegaserod were associated with serious cardiac risks. They were pulled from the market because of this.   

Prucalopride is used to treat constipation that doesn't respond to other treatments. It has not shown the cardiac side effects that happened with cisapride and tegaserod.

Macrolides. These are antibiotics that also act as prokinetic agents. Azithromycin and erythromycin have been shown to help gastroparesis. However, there are problems associated with long-term antibiotic use. Because of problems with antibiotic resistance, using macrolides as a prokinetic agent should be avoided.   

Using prokinetic agents to treat disorders caused by problems with peristalsis has not been very effective in many cases. Gastroesophageal reflux disease (GERD) is now treated with other types of medicines such as proton pump inhibitors (PPIs). PPIs work by reducing the amount of stomach acid your body produces.

Additionally, all of these prokinetic agents can have side effects, especially when used for a long time. Some side effects of common prokinetic agents include: