COMT (catechol-o-methyl transferase) inhibitors are a class of medications that doctors use in combination with levodopa to treat the motor symptoms of Parkinson’s disease. COMT inhibitors work by blocking the action of enzymes that break down levodopa, to extend the time of levodopa activity.

Doctors may combine COMT inhibitors with monoamine oxidase B (MAO-B) inhibitors, which also extend the action of levodopa but work through a different mechanism.

How do COMT inhibitors work?

Parkinson’s disease is characterized by a lack of the neurotransmitter or cell-signaling molecule dopamine. Because dopamine itself cannot cross the blood-brain barrier, doctors use levodopa to compensate for the missing dopamine to treat the disease. Levodopa can cross this blood barrier, and once inside the brain be converted into dopamine.

COMT are enzymes that break down levodopa, limiting the amount delivered to the brain. COMT inhibitors suppress the activity of COMT enzymes, subsequently extending the window of time in which levodopa is active. This reduces the occurrence of “off” episodes (the time between levodopa doses when motor symptoms recur).

Many patients also can lower the levodopa dose they need by combining the medication with a COMT inhibitor. Because high doses of levodopa may cause dyskinesia (involuntary, uncontrolled movements), a lower dose is considered better.

Types of COMT inhibitors for Parkinson’s

Comtan (entacapone) and Tasmar (tolcapone) are two COMT inhibitors that doctors use to treat Parkinson’s disease. Tasmar is more potent than Comtan, but may cause liver damage.

The European Commission approved a new once-daily oral COMT inhibitor, Ongentys (opicapone), in 2016. The U.S. Food and Drug Administration (FDA) also approved Ongentys in April 2020 after two successful Phase 3 clinical trials (BIPARK-I, NCT01568073, and BIPARK-II NCT01227655).

Ongentys has a very high binding affinity to the COMT enzyme, which results in a long duration of action. This allows physicians to lower the dose of levodopa further and reduce off episodes.

Other information

Common side effects of COMT inhibitors include loss of appetite, sleeping problems, dizziness, hallucinations, diarrhea, and headaches.

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