What Are COMT Inhibitors?

COMT (catechol-O-methyltransferase) inhibitors are a class of drugs used along with carbidopa-levodopa therapy to treat the symptoms of Parkinson’s disease (PD). Carbidopa-levodopa therapy is the most effective drug available to treat the motor symptoms of PD. However, over time people experience less effect from the medicine. COMT inhibitors can extend the effectiveness of carbidopa-levodopa therapy. They also allow for lower doses of carbidopa-levodopa.1,2

COMT inhibitors may reduce the motor fluctuation seen in many people with PD. Fluctuating symptoms of carbidopa-levodopa therapy are described as "on" and "off" episodes. "On" episodes are when the medicine is working and symptoms are minimal. "Off" episodes are when the medicine has not yet taken effect or is wearing off and symptoms are worsened. "Off" episodes can interfere with daily activities and may be experienced multiple times a day. They may last a few minutes or as long as a few hours.1,2

How do COMT inhibitors work?

COMT is an enzyme that breaks down neurotransmitters (chemical messengers) like dopamine. COMT inhibitors block the action of the COMT enzyme. The motor symptoms of Parkinson’s are caused by the reduction in dopamine, which transmits signals in the brain to produce smooth, purposeful movement. As PD damages and destroys the neurons (nerve cells) that produce dopamine, the motor symptoms of PD appear.

Levodopa therapy provides the precursor to dopamine. It is the substance used to make dopamine. Adding a COMT inhibitor slows the breakdown of levodopa in the body. This allows more of it to get into the brain, thus increasing its effects.3,4

Examples of COMT inhibitors

The 3 COMT inhibitors used in the treatment of PD are:1

  • Comtan® (entacapone)
  • Tasmar® (tolcapone)
  • Ongentys® (opicapone)

These drugs are prescribed along with carbidopa-levodopa therapy.1

Side effects

Side effects can vary depending on the specific drug you are taking. The most common side effects of COMT inhibitors include:1

Tolcapone may cause potentially fatal liver failure. Because of this serious side effect, it should only be considered for people who are not getting enough symptom control or candidates for other therapies.1,5

These are not all the possible side effects of COMT inhibitors. Talk to your doctor about what to expect or if you experience any changes that concern you during treatment with COMT inhibitors.

Things to know

Because COMT inhibitors and non-selective MAO-B (monoamine oxidase-B) inhibitors work in similar ways, they should not be taken at the same time. COMT inhibitors may be used along with selective MAO-B inhibitors, such as:5,6

  • Safinamide (Xadago®)
  • Selegiline (Eldepryl®, Carbex®, Zelapar®)
  • Rasagiline (brand name Azilect®)

It is important for people with PD to see a movement disorders specialist who is trained in the use of these drugs for PD. They understand the interactions of these drugs and how some medicines may make symptoms worse.

Before beginning treatment for Parkinson's disease, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.

Additional therapy

Besides COMT inhibitors, there are several different types of treatment for the symptoms of PD, including:

Each person with PD experiences a unique set of symptoms and progression of the disease. Treatments are based on the person's symptoms and how they respond to different drugs.

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Written by: Emily Downward and Heather Morse | Last reviewed: May 2021