title: L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment.
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.
authors.affiliation: Department of Drug Sciences,G. d'Annunzio University, Faculty of Pharmacy, Chieti, Italy. adistefano@unich.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stefano
authors.forename: Piera
authors.initials: P
authors.lastname: Sozio
authors.forename: Laura Serafina
authors.initials: LS
authors.lastname: Cerasa
authors.forename: Antonio
authors.initials: A
authors.lastname: Iannitelli
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015394:Molecular Structure; D010300:Parkinson Disease / Q000188:drug therapy*; D011355:Prodrugs / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D011355:Prodrugs; D007980:Levodopa