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 b enserazide, for the treatment of Parkinson's disease, it became eviden t that several disturbing side effects were limiting the therapeutic e fficacy of this amino acid. This paper discusses novel practical appro aches for the management of these levodopa-related complications. Thes e approaches include therapeutic strategies for controlled delivery of levodopa to the brain (controlled-release preparations), rescue treat ment with subcutaneous, intranasal, or sublingual administration of th e dopamine agonist apomorhine, and the administration of an atypical n euroleptic, such as clozapine. Other approaches for prolonging the res ponse of levodopa that are being used or investigated are also reviewe d in this paper. These include the use of levodopa prodrugs and blocki ng the degradation in the brain with inhibitors of monoamine oxidase-B and catechol-O-methyltransferase.