Medicine & USMLE

Entacapone, Tolcapone

Other Neuro Pharm
  1. Ramelteon
  2. Triptans
  3. Benzodiazepines - Function
  4. Zolpidem Zaleplon Eszopiclone
  5. Suvorexant
  6. Bromocriptine (Ergot Dopamine Agonists)
  7. Pramipexole, Ropinirole
  8. Amantadine
  9. Levodopa, Carbidopa
  10. Entacapone, Tolcapone
  11. Selegiline and Rasagiline
  12. Benztropine, Trihexyphenidyl
  13. Tetrabenazine
  14. Baclofen
  15. Memantine
  16. Riluzole
  17. Full Opioid Agonists
  18. Partial Opioid Agonists
  19. Dextromethorphan
  20. Tramadol
  21. Naloxone
  22. Naltrexone


Entacapone and Tolcapone are drugs used in the treatment of Parkinson's disease. They inhibit the enzyme COMT to increase the availability of levodopa or L-DOPA, a precursor to dopamine in the brain. Importantly, entacapone cannot cross the blood brain barrier, so it only works peripherally. In contrast, tolcapone can cross the blood-brain barrier, so it works both peripherally and centrally to increase levodopa availability. This increase in levodopa concentrations in turn increases dopamine levels, which helps to treat Parkinson’s disease. Know that Entacapone and Tolcapone must be used in conjunction with levodopa in order to be effective. A major side effect of tolcapone that is not seen with entacapone is hepatotoxicity. 

Key Points

  • Entacapone, Tolcapone 
    • Drug Names
      • -capone drugs (entacapone, tolcapone)
    • Mechanism
      • Catechol-O-methyltransferase (COMT)  inhibitor: increases levodopa availability in brain
        • Entacapone: peripheral only
        • Tolcapone: peripheral + central
          • Decreases breakdown of levodopa
            • Prevents peripheral L-DOPA degradation to 3-O-methyldopa by inhibiting catechol-o-methyltransferase
          • Blocks breakdown of dopamine in CNS (combats “wearing off” effect)
            • Blocks conversion of dopamine to 3-methoxytyramine (3-MT) by inhibiting COMT in the CNS
    • Clinical Use
      • Parkinson’s disease 
        • Only when given in conjunction with levodopa
    • Adverse Effects
      • Hepatotoxicity (tolcapone only)