L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment

Curr Pharm Des. 2011;17(32):3482-93. doi: 10.2174/138161211798194495.

Abstract

L-Dopa is the mainstay of Parkinson's 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 drug's 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Design*
  • Humans
  • Levodopa / adverse effects
  • Levodopa / chemistry
  • Levodopa / pharmacokinetics
  • Levodopa / therapeutic use*
  • Molecular Structure
  • Parkinson Disease / drug therapy*
  • Prodrugs / adverse effects
  • Prodrugs / chemistry
  • Prodrugs / pharmacokinetics
  • Prodrugs / therapeutic use*
  • Structure-Activity Relationship

Substances

  • Prodrugs
  • Levodopa