Abstract
L-Dopa is the mainstay of Parkinsons disease therapy; this drug is usually administered orally, but it is extensively metabolized in the gastrointestinal tract, so that relatively little arrives in the bloodstream as intact L-Dopa. The peripheral conversion of L-Dopa by amino acid decarboxylase to dopamine is responsible for the typical gastrointestinal and cardiovascular side effects. To minimize the conversion to dopamine outside the central nervous system, L-Dopa is usually given in combination with peripheral inhibitors of amino acid decarboxylase. In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for the poor bioavailability are the drugs physical-chemical properties: low water and lipid solubility, resulting in unfavorable partition, and the high susceptibility to chemical and enzymatic degradation. Starting from these considerations the prodrug approach has been applied to L-Dopa in order to overcome its metabolism problems and to improve its bioavailability. The goal of this paper is to provide the reader with a critical overview on L-Dopa prodrugs here classified according to the nature of the main chemical modification on L-Dopa backbone that led to the formation of the desired derivative.
Keywords: Parkinson's disease, L-dopa, dopamine, prodrugs, codrugs, antiparkinson, dyskinesia, plasma, chronic oxidative stress, cell death
Current Pharmaceutical Design
Title: L-Dopa Prodrugs: An Overview of Trends for Improving Parkinsons Disease Treatment
Volume: 17 Issue: 32
Author(s): Antonio Di Stefano, Piera Sozio, Laura Serafina Cerasa and Antonio Iannitelli
Affiliation:
Keywords: Parkinson's disease, L-dopa, dopamine, prodrugs, codrugs, antiparkinson, dyskinesia, plasma, chronic oxidative stress, cell death
Abstract: L-Dopa is the mainstay of Parkinsons disease therapy; this drug is usually administered orally, but it is extensively metabolized in the gastrointestinal tract, so that relatively little arrives in the bloodstream as intact L-Dopa. The peripheral conversion of L-Dopa by amino acid decarboxylase to dopamine is responsible for the typical gastrointestinal and cardiovascular side effects. To minimize the conversion to dopamine outside the central nervous system, L-Dopa is usually given in combination with peripheral inhibitors of amino acid decarboxylase. In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for the poor bioavailability are the drugs physical-chemical properties: low water and lipid solubility, resulting in unfavorable partition, and the high susceptibility to chemical and enzymatic degradation. Starting from these considerations the prodrug approach has been applied to L-Dopa in order to overcome its metabolism problems and to improve its bioavailability. The goal of this paper is to provide the reader with a critical overview on L-Dopa prodrugs here classified according to the nature of the main chemical modification on L-Dopa backbone that led to the formation of the desired derivative.
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Cite this article as:
Di Stefano Antonio, Sozio Piera, Serafina Cerasa Laura and Iannitelli Antonio, L-Dopa Prodrugs: An Overview of Trends for Improving Parkinsons Disease Treatment, Current Pharmaceutical Design 2011; 17 (32) . https://dx.doi.org/10.2174/138161211798194495
DOI https://dx.doi.org/10.2174/138161211798194495 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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