COMT (catechol-o-methyl transferase) inhibitors are a class of medications used in combination with levodopa to treat the motor symptoms of Parkinson’s disease. COMT inhibitors block the action of enzymes that break down levodopa and thereby extend the time of levodopa activity.
How 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, levodopa is used to compensate for the missing dopamine to treat the disease. Levodopa can cross the blood-barrier and once inside the brain it is converted into dopamine.
COMT are enzymes that break down levodopa, limiting its delivery to the brain. COMT inhibitors suppress the activity of COMT enzymes, subsequently extending the time window 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 of the medication is preferred.
Types of COMT inhibitors for Parkinson’s disease
A new once-daily oral COMT inhibitor, Ongentys (opicapone) is currently in clinical trials. 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.
Ongentys was approved by the European Commission in 2016. After two successful Phase 3 clinical trials (BIPARK-I, NCT01568073, and BIPARK-II NCT01227655), Neurocrine Biosciences, the developer of Ongentys, plans to ask the U. S. Food and Drug Administration (FDA) to initiate a regulatory review process that could lead to approval of Ongentys as a treatment for Parkinson’s disease.
Common side effects of COMT inhibitors include loss of appetite, sleeping problems, dizziness, hallucinations, diarrhea, and headaches.
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