USMLE

Entacapone, Tolcapone

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Summary

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)