COMT inhibitors

How do they work?

COMT (short for catechol-O-methyltransferase) inhibitors, e.g., entacapone, tolcapone, are always given with levodopa, and never alone. This is because they prevent levodopa from being broken down before it gets to the brain (see Figure, below).

What are the benefits?

When people with Parkinson’s disease (PD) begin to experience end of dose wearing off with levodopa treatment, a COMT inhibitor can be added to decrease OFF time, and reduce fluctuations – improving the response to levodopa. In such cases, the levodopa dose may need to be reduced.

What are the side effects?

COMT inhibitors generally produce few side effects, and those that do occur are usually caused by the increasing dopamine levels produced by the medications. Entacapone may cause dyskinesia, nausea, hallucinations, urine discolouration, diarrhoea, and stomach pain. However, these effects are often reduced by lowering the levodopa dose. Diarrhoea lasting longer than 2 weeks should be reported to a doctor.

Tolcapone has been associated with adverse effects on the liver (hepatotoxicity), and therefore liver monitoring is required while taking this medication.

How COMT inhibitors work

(Click on animation to enlarge.)