A 55-year-old man has Parkinson's disease with wearing-off and on-off fluctuations despite optimised levodopa-carbidopa regimen. An 'off' state UPDRS motor score is 42/108. His neurologist considers adjunct therapy. Which agent acts by inhibiting catechol-O-methyltransferase (COMT) peripherally AND centrally, allowing better central levodopa bioavailability?
- A Entacapone (peripheral COMT inhibitor)
- B Opicapone (peripheral COMT inhibitor, once daily)
- C Tolcapone (peripheral and central COMT inhibitor) ✓
- D Rasagiline (MAO-B inhibitor)
Explanation
Tolcapone is a COMT inhibitor that, unlike entacapone and opicapone, crosses the blood-brain barrier and inhibits COMT both peripherally and centrally. This dual action provides more comprehensive inhibition of levodopa degradation, resulting in a greater and more sustained increase in central dopaminergic tone. However, tolcapone is associated with rare but severe hepatotoxicity (requiring liver function monitoring), which limits its use to patients who fail or cannot tolerate entacapone. Entacapone and opicapone are peripheral-only COMT inhibitors. Rasagiline is a selective, irreversible MAO-B inhibitor with different mechanism.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.