Entacapone is co-administered with Madopar to achieve what pharmacologic effect?

• A. Inhibit COMT to increase levodopa availability
• B. Inhibit MAO-B
• C. Block acetylcholine receptors
• D. Increase dopamine release

Answer: (A)

Entacapone works by inhibiting an enzyme in the periphery that normally breaks down levodopa before it reaches the brain. When Madopar (levodopa with carbidopa) is given, a portion of levodopa is metabolized by catechol-O-methyltransferase (COMT), forming products that don’t contribute to brain dopamine and that reduce the amount of active drug entering the CNS. By blocking COMT, entacapone slows this peripheral metabolism, increasing levodopa plasma levels and allowing more to reach the brain. This prolongs the antiparkinsonian effect and helps reduce wearing-off fluctuations. This mechanism is distinct from MAO-B inhibition (which prevents dopamine breakdown inside the brain), cholinergic receptor blockade, or directly increasing dopamine release; entacapone’s main action is to keep more levodopa available by inhibiting COMT.