Levodopa in Parkinson's Disease: Current Status and Future Developments

Current Neuropharmacology
Nicola TambascoPaolo Calabresi

Abstract

Ever since the pioneering reports in the 60s, L-3,4-Dioxyphenylalanine (levodopa) has represented the gold standard for the treatment of Parkinson's Disease (PD). However, long-term levodopa (LD) treatment is frequently associated with fluctuations in motor response with serious impact on patient quality of life. The pharmacokinetic and pharmacodynamic properties of LD are pivotal to such motor fluctuations: discontinuous drug delivery, short half-life, poor bioavailability, and narrow therapeutic window are all crucial for such fluctuations. During the last 60 years, several attempts have been made to improve LD treatment and avoid long-term complications. Research and trials to improve the LD pharmacokinetic since 1960s are reviewed, summarizing the progressive improvements of LD treatment. Inhibitors of peripheral amino acid decarboxylase (AADC) have been introduced to achieve proper LD concentration in the central nervous system reducing systemic adverse events. Inhibitors of catechol-O-methyltransferase (COMT) increased LD half-life and bioavailability. Efforts are still being made to achieve a continuous dopaminergic stimulation, with the combination of oral LD with an AADC inhibitor and a COMT inhibitor, or the intra-duo...Continue Reading

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Clinical Trials Mentioned

NCT02605434
NCT02577523
NCT02726386
NCT02782481
NCT02240030
NCT02242487

Software Mentioned

My Flexible Individual Dosing , MyFid
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