Entacapone may be useful in patients being treated with levodopa-carbidopa combination because it :
Levodopa is converted to dopamine by dopa decarboxylase (that cannot cross the blood-brain barrier).
Carbidopa is an inhibitor of dopa decarboxylase in the periphery. It therefore increases the amount of l-dopa that reaches the brain (due to inhibition of peripheral metabolism to dopamine).
Due to inhibition of l-dopa metabolism (by dopa decarboxylase), an alternative pathway of metabolism by catechol-O-methyl transferase (COMT) is activated.
COMT metabolizes l-dopa to 3-O-methyldopa (3-OMD) that can complete with l-dopa for entry in the brain.
Entacapone and tolcapone is useful in Parkinsonism by inhibiting COMT.
Activates COMT
Decreases formation of 3–OMD
Inhibits monoamine oxidase type B
Inhibits dopamine uptake