Catechol-O-methyl transferase (COMT) inhibitors block the peripheral metabolism 
of levodopa, increase its plasma half-life, and enhance its brain availability. 
Two COMT inhibitors, tolcapone and entacapone, have recently been made available 
as adjunctive agents to levodopa. In PD patients with motor fluctuations, they 
have been shown to increase "on" time and reduce "off" time. In patients with 
more advanced disease, they provide similar benefits, but patients tend to 
experience less overall benefit and a greater likelihood of developing 
dopaminergic adverse events. Accordingly, closer monitoring is required. In 
stable patients who have not yet developed motor complications, there are 
preliminary data suggesting that they experience improvements in motor function 
and in activities of daily living. Finally, there are theoretical reasons to 
consider administering a COMT inhibitor to patients from the onset of levodopa 
therapy in order to reduce the likelihood that motor complications will develop. 
COMT inhibitors are easy to administer, do not require titration, and are 
generally well tolerated particularly in patients with relatively mild disease. 
Adverse events are primarily dopaminergic and can usually be controlled by 
levodopa dose adjustments. COMT inhibitors have thus proven to be a useful 
addition to the therapeutic armamentarium of PD.