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Prokinetic Agents

Prokinetic agents are a class of drugs that help with gut motility — the muscle contractions that move food forward throughout your GI tract. But many come with a high risk of neurological and heart-related side effects. For this reason, many prokinetic agents are no longer available in the U.S.

Overview

What is a prokinetic agent?

Prokinetic agents are drugs that stimulate contractions along your gastrointestinal (GI) tract. They help move food along. When you swallow food, the muscles in your GI tract start to contract. This involuntary muscle movement is called peristalsis. The muscles move food down your throat to your esophagus (food tube), stomach and intestines. The contractions allow your body to absorb nutrients along the way.

Conditions that interfere with peristalsis can cause unpleasant symptoms, like constipation or heartburn. Food may sit in your stomach for too long, and you may not get the nutrition you need.

Prokinetic agents help get your gut moving, but they’re associated with significant side effects. Typically, healthcare providers prescribe other drugs, like proton pump inhibitors (PPIs) or H2 blockers, before prescribing prokinetic agents. Still, depending on your diagnosis, your provider may recommend a prokinetic agent.

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How do prokinetic agents work?

Prokinetic agents work by getting the nerves in your gut to contract. Prokinetic agents:

  • Increase contractions in your esophagus to move food to your stomach.
  • Strengthen your lower esophageal sphincter (LES). Your LES connects your esophagus to your stomach. If it’s too relaxed or opens when it’s not supposed to, stomach acid can seep into your esophagus and throat. The result is a burning sensation (heartburn) associated with acid reflux (GERD).
  • Increase contractions in your stomach to move food to your intestines.
  • Decrease the time it takes for your stomach to empty (this means less stomach contents can seep back up into your esophagus, as with acid reflux).

What conditions do prokinetic agents treat?

Prokinetic agents treat:

  • Gastroparesis (paralysis of the stomach): With gastroparesis, weak stomach muscle contractions delay digestion. Prokinetic drugs promote contractions, so your stomach empties faster. Your provider may recommend taking the prokinetic agent metoclopramide if other treatments haven’t helped. Metoclopramide is the only FDA-approved medicine for gastroparesis, including gastroparesis related to diabetes (diabetic gastroparesis).
  • GERD (chronic acid reflux): GERD involves stomach acid flowing from your stomach back up through your esophagus and into your mouth. This can happen if your LES opens when it shouldn’t or isn’t sealed enough. Prokinetic agents alone don’t help with GERD. Your provider may prescribe them alongside other treatments if your condition involves your stomach not emptying fast enough.
  • Functional dyspepsia (chronic indigestion): Functional dyspepsia involves having ongoing symptoms of indigestion after meals but not knowing why. Prokinetic agents help people experience symptom relief in some cases. Researchers suggest that the drugs increase stomach contractions, so it empties faster.
  • Nausea and vomiting: If you have acute (sudden) or chronic (long-term) vomiting and other treatments haven’t worked, your provider may prescribe a prokinetic agent. This includes treatments for vomiting related to taking chemotherapy drugs.
  • Chronic intestinal pseudo-obstruction: With this condition, you experience the symptoms of having bowel obstruction — but you don’t actually have a blockage. Researchers are currently studying the role some prokinetic agents may have in providing symptom relief.

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What are the types of prokinetic drugs?

Prokinetic drug types include agonists and antagonists.

  • Agonists mimic the behavior of certain neurotransmitters. Neurotransmitters are chemical messengers that attach to a nerve and tell it what to do. Agonists behave as neurotransmitters that attach to a nerve and tell it to contract.
  • Antagonists prevent certain neurotransmitters from binding to a nerve. They prevent neurotransmitter messengers that interfere in peristalsis from attaching.

Different categories of prokinetic agents include:

  • Cholinergic agonists. These drugs mimic acetylcholine, a neurotransmitter that stimulates your intestinal muscles to contract. Examples include baclofen, bethanechol, neostigmine and pyridostigmine.
  • Motilin agonists (macrolide antibiotics). These drugs mimic motilin, a neurotransmitter that stimulates contractions in your small intestine. They include drugs that are typically used as antibiotics to treat bacterial infections. Examples include erythromycin and azithromycin.
  • Serotonin agonists. These drugs mimic the serotonin neurotransmitter. Like serotonin, they stimulate contractions in your intestines and help your stomach empty. Examples include cisapride, prucalopride and tegaserod.
  • Dopamine antagonists. Dopamine antagonists prevent dopamine from binding to nerve cells. Dopamine reduces movement in your stomach and intestines. It causes your LES to relax. By preventing dopamine from binding, dopamine antagonists counter this effect. Examples include metoclopramide and domperidone.

Examples of prokinetic agents

Prescription prokinetic drugs include medicines currently used for treatment (like metoclopramide for gastroparesis), drugs that are no longer available in the U.S. because of side effects, and drugs currently being studied for safety and effectiveness.

Examples of prokinetic agents include:

  • Azithromycin (Zithromax®): Motolin agonist that may be prescribed off-label to treat gastroparesis.
  • Baclofen (ED baclofen®): Cholinergic agonist that’s currently being studied for its benefits in treating GERD that doesn’t respond to PPI treatment.
  • Bethanechol (Urecholine®): Cholinergic agonist that helps with gastroparesis and relieves GERD symptoms. It can cause serious side effects, though, like involuntary muscle movements and blurred vision, which means it isn’t prescribed a lot.
  • Cisapride (Propulsid®): Serotonin agonist that helps your stomach empty faster. It was once used as a treatment for GERD. Cisapride was removed from the market in the U.S. because of heart-related side effects.
  • Domperidone (Motilium®): Dopamine antagonist that’s not available in the U.S. unless healthcare providers apply to the FDA for expanded access to prescribe it. Side effects include serious heart problems, including an irregular heartbeat or heart attack.
  • Erythromycin (E.E.S.®): Motolin agonist that a healthcare provider may prescribe off-label to treat gastroparesis.
  • Metoclopramide (Reglan®, Maxeran®, Gimoti®): Dopamine antagonist that’s the only FDA-approved medication to treat gastroparesis. It also treats GERD that hasn’t responded to typical treatments. However, it comes with a warning that it may cause nervous system side effects.
  • Prucalopride (Motegrity®): Serotonin agonist that treats chronic constipation. It can also help your stomach empty faster.
  • Pyridostigmine (Mestinon®): Cholinergic agonist that primarily treats myasthenia gravis, but it’s sometimes used to treat gastroparesis.

What are the side effects of taking prokinetic agents?

Prokinetic agents can cause serious side effects that prevent healthcare providers from prescribing them. Still, your provider may recommend a prokinetic agent when typical treatments (like PPIs for GERD) aren’t helping. Or, your provider may prescribe a prokinetic agent at a low dose or for a limited time as a safety measure.

If your healthcare provider prescribes a prokinetic agent, ask about the specific side effects associated with that drug.

Side effects include:

Cisapride, domperidone and tegaserod were all pulled from the market because of the risk of serious heart problems, including:

Research into new prokinetic agents focuses on developing drugs that provide the benefits of promoting contractions in your gut — without putting you at risk of side effects.

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Additional Common Questions

What are the most common prokinetic agents?

The most commonly prescribed prokinetic agents are metoclopramide and domperidone. In the U.S., metoclopramide is the only FDA-approved treatment for gastroparesis. But your provider can request the FDA grant them permission to prescribe domperidone.

A note from Cleveland Clinic

Prokinetic agents vary in terms of their effectiveness and safety when it comes to treating digestive system conditions. Your healthcare provider may try other medications before trying a prokinetic agent because of the risk of side effects. Still, if you’re experiencing severe symptoms because your GI tract isn’t contracting, a prokinetic agent may bring much-needed relief. Your healthcare provider can help you understand potential benefits and risks if you’re taking a prokinetic agent.

Medically Reviewed

Last reviewed on 04/26/2024.

Learn more about our editorial process.

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