Entacapone, a COMT inhibitor used in Parkinson's disease as an adjunct to levodopa, exerts its therapeutic benefit by:

• A Inhibiting MAO-B to prevent dopamine breakdown in the striatum
• B Stimulating dopamine D2 receptors directly in the substantia nigra
• C Inhibiting aromatic amino acid decarboxylase in the periphery
• D Blocking peripheral COMT, preventing O-methylation of levodopa and extending its plasma half-life ✓

Explanation

Catechol-O-methyltransferase (COMT) in the gut wall and liver converts levodopa to 3-O-methyldopa (3-OMD), reducing levodopa bioavailability and competing with levodopa for brain transport. Entacapone inhibits peripheral COMT, preventing this O-methylation, thereby increasing the area under the levodopa plasma curve and extending 'on' time. Entacapone does not cross the BBB and does not inhibit central COMT, unlike tolcapone. Carbidopa inhibits peripheral AAAD; selegiline inhibits MAO-B.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.