[Tolcapone: a different, effective approach to improving dopaminergic treatment in Parkinson's disease]

Tolcapone is a potent, selective, reversible inhibitor of COMT. Coadministration of tolcapone with levodopa and a decarboxylase inhibitor prolongs the elimination half-life of levodopa and reduces the formation of 3-0-metildopa in a dose-dependent form. The improvement in the pharmacokinetics of levodopa prolongs the motor effects of levodopa. Clinical studies have shown that the concomitant administration of levodopa and tolcapone is effective on the management of the wearing-off phenomenon. Tolcapone can significantly reduce the off time and increases the total on time while simultaneously reducing levodopa dosage and frequency. Most adverse events are dopaminergic in nature and related to the increase in levodopa bioavailability. Dyskinesias may increase in frequency and severity in patients already having dyskinesias and these may appear for the first time after adding tolcapone in patients at risk. Diarrhoea is the main nondopaminergic adverse event leading to the stop of the drug in less than 10% of cases. Taking into account that tolcapone significantly enhance the action of levodopa, it would be wise to reduce the total daily dose of levodopa at the same time that tolcapone is introduced. No tolerance effect was observed in 12-month studies. Tolcapone can be used with standard or sustained release levodopa, and, when appropriate, in conjunction with dopamine agonists or selegiline.