Two inhibitors of catechol-O-methyl transferase (COMT), tolcapone and 
entacapone, have recently been introduced as adjuncts to levodopa in the 
treatment of Parkinson's disease patients. Both have been shown to provide PD 
patients with increased "on" time, decreased "off" time, and improved motor 
scores. There are, however, a number of practical issues that must be considered 
in order to achieve maximal benefits with this class of agent. They include 
dosing and administration, efficacy, adverse events, and patient education. In 
general, these agents are easy to administer and well tolerated. Both the 
benefits and the principal side effects of treatment are related to increased 
dopaminergic activity. Patients must be advised of possible side effects so that 
they can be reported in a timely manner. Physicians must appreciate that 
dopaminergic side effects, such as dyskinesia, should be controlled by adjusting 
the dose of levodopa and not the COMT inhibitor. Explosive diarrhea has been 
reported with tolcapone and usually necessitates discontinuing the drug. 
Tolcapone must also be monitored for possible liver dysfunction. This has not 
been reported with entacapone, and no monitoring is required. Metabolites of 
tolcapone and entacapone may cause discoloration of the urine. This is harmless 
but patients should be advised that this may occur.