Catechol-O-methyltransferase inhibitors in the management of Parkinson's disease

Parkinson's disease is the most common neurodegenerative disease in which t he chemical pathology is known and effective symptomatic treatment, levodop a, is available. Therapy in the initial years after initiation with dopa de carboxylase inhibitors, carbidopa or benserazide, combined with levodopa re sults in favorable, stable responses. However, by 5 years after the initiat ion of treatment, over two thirds of patients experience motor fluctuations beginning initially with a "wearing-off" effect followed by more complex f luctuations including dyskinesias and "on-off" responses. A number of strat egies have been developed in an attempt to deal with these complications in cluding changing doses and frequencies, adding agonist medications, adding or substituting controlled-release levodopa, and surgical therapies. A more recent strategy has centered on increasing the availability of intracellul ar levodopa and synaptic dopamine by inhibiting the peripheral and central metabolism of levodopa to 3-O-methyldopa with the use of a catechol-O-methy ltransferase inhibitor. To date, two of these inhibitors, tolcapone and ent acapone, are available to treat the wearing-off phase of levodopa therapy.