Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), that in combination with carbidopa and levodopa used for the treatment of Parkinson's disease. Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD). When entacapone is given in conjunction with levodopa and carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and carbidopa alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson’s disease. The higher levodopa levels may also lead to increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa. When 200 mg entacapone is coadministered with levodopa/carbidopa, it increases levodopa plasma exposure (AUC) by 35-40% and prolongs its elimination half-life in Parkinson’s disease patients from 1.3 to 2.4 hours. Plasma levels of the major COMT-mediated dopamine metabolite, 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD), are also markedly decreased proportionally with increasing dose of entacapone. In animals, while entacapone enters the CNS to a minimal extent, it has been shown to inhibit central COMT activity. In humans, entacapone inhibits the COMT enzyme in peripheral tissues. The effects of entacapone on central COMT activity in humans have not been studied.