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What Are COMT Inhibitors?

COMT (catechol-O-methyltransferase) inhibitors are a class of medications that are used along with carbidopa-levodopa therapy in the treatment of symptoms of Parkinson’s disease (PD). Carbidopa-levodopa therapy is the most effective medication for alleviating the motor symptoms of PD; however, over time people experience less effect from the medication. COMT inhibitors can extend the effectiveness of carbidopa-levodopa therapy, and allow for lower doses of carbidopa-levodopa.1,2

COMT inhibitors can help reduce the fluctuation of symptoms that many people being treated with carbidopa-levodopa experience. Fluctuating symptoms of carbidopa-levodopa therapy are described as “on” and “off” episodes. “On” episodes are experienced when medication is working and symptoms are minimal, and “off” episodes are when the medication hasn’t 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 COMT inhibitors work

COMT is an enzyme that metabolizes or degrades neurotransmitters such as 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 that is used to make dopamine. Adding a COMT inhibitor slows the breakdown of levodopa in the body, making more of it available to get in the brain, thus increasing its effects.3,4

Because COMT inhibitors and non-selective MAO-B (monoamine oxidase-B) inhibitors are believed to have similar mechanisms of action, they should not be taken at the same time. COMT inhibitors may be used in combination with selective MAO-B inhibitors, such as safinamide (brand name Xadago®), selegiline (brand names Eldepryl®, Carbex®, Zelapar®) and rasagiline (brand name Azilect®).5,6

Formulations of COMT inhibitors

The two COMT inhibitors used in the treatment of PD are Comtan® (entacapone) and Tasmar® (tolcapone). Both are available in tablet form. These medications are prescribed in conjunction with carbidopa-levodopa therapy.1

Side effects of COMT inhibitors

Each medication has its own set of possible side effects; however, side effects commonly experienced by people taking COMT inhibitors include abdominal pain, back pain, constipation, nausea, diarrhea, and blood in the urine.1

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

It is important for people with PD to see a movement disorders specialist who is trained in the use of these drugs for PD. Movement disorders specialists understand the interactions of these drugs and how some medications may make symptoms worse. It is also important to talk with your healthcare provider before starting or stopping any new treatments, including over-the-counter medications and alternative treatments.

Additional therapy

Besides COMT inhibitors, there are several different types of treatment for the symptoms of PD, including carbidopa-levodopa therapy, dopamine agonists, anticholinergics, MAO-B inhibitors, and surgery for deep brain stimulation. Each person with PD experiences a highly individual set of symptoms and progression of the disease. Treatments are determined based on the individual’s symptoms and how they respond to different medications.

Written by: Emily Downward | Last reviewed: October 2019
  1. Parkinson’s Disease Foundation. Accessed online on 1/23/17 at
  2. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014 Apr 23-30;311(16):1670-83.
  3. National Center for Biotechnology Information, National Institutes of Health. Accessed online on 1/23/17 at
  4. National Parkinson Foundation. Accessed online on 1/23/17 at
  5. Tasmar prescribing information. Accessed online on 1/23/17 at
  6. Finberg JPM, Rabey JM. Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology. Frontiers in Pharmacology. 2016;7:340. doi:10.3389/fphar.2016.00340.