New and emerging strategies for improving levodopa treatment.

Soon after the successful introduction of large oral doses of levodopa or of levodopa plus a decarboxylase inhibitor, such as carbidopa or benserazide, for the treatment of Parkinson's disease, it became evident that several disturbing side effects were limiting the therapeutic efficacy of this amino acid. This paper discusses novel practical approaches for the management of these levodopa-related complications. These approaches include therapeutic strategies for controlled delivery of levodopa to the brain (controlled-release preparations), rescue treatment with subcutaneous, intranasal, or sublingual administration of the dopamine agonist apomorphine, and the administration of an atypical neuroleptic, such as clozapine. Other approaches for prolonging the response of levodopa that are being used or investigated are also reviewed in this paper. These include the use of levodopa prodrugs and blocking the degradation in the brain with inhibitors of monoamine oxidase-B and catechol-O-methyltransferase.