Entacapone is a potent and specific peripheral catechol-O-methyltransferase 
(COMT) inhibitor. It has been shown to improve the clinical benefits of levodopa 
plus an aromatic L-amino acid decarboxylase inhibitor (AADC) when given to 
patients with Parkinson's disease and end-of-dose deterioration in the response 
to levodopa (the 'wearing off' phenomenon). The efficacy of entacapone is 
currently being assessed in patients with stable Parkinson's disease. In 2 well 
conducted trials of 6 months' duration and smaller short term studies, treatment 
with entacapone (200 mg with each dose of levodopa/AADC inhibitor) was 
associated with significant increases in daily 'on' time and decreases in 'off' 
time. Changes in Unified Parkinson's Disease Rating Scale (UPDRS) scores 
concurred with changes in 'on' and 'off' times: entacapone improved total, 
activities of daily living and motor function scores, but it had no effect on 
mentation scores. Entacapone also provided benefits when given with controlled 
release levodopa/ AADC inhibitor or with standard levodopa/AADC inhibitor and 
selegiline in small trials. Dopaminergic events, including dyskinesia and 
nausea, are among the most common events with entacapone, and are related to the 
drug's ability to potentiate the effects of levodopa. Diarrhoea, abdominal pain, 
constipation and urine discolouration are the most common nondopaminergic 
events, although the latter event is the only one to occur consistently more 
frequently with entacapone than with placebo. However, adverse events of any 
type infrequently led to study discontinuation.
CONCLUSIONS: The efficacy and tolerability of entacapone administered with 
levodopa/AADC inhibitor have not yet been compared with those of other 
strategies for the treatment of Parkinson's disease. However, once the decision 
to initiate levodopa therapy has been made, studies generally support the use of 
entacapone as an adjunct to levodopa in patients with Parkinson's disease and 
the 'wearing off' phenomenon.