L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment.
Curr Pharm Des
; 17(32): 3482-93, 2011.
Article
en En
| MEDLINE
| ID: mdl-22074421
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Profármacos
/
Diseño de Fármacos
/
Levodopa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Pharm Des
Asunto de la revista:
FARMACIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Emiratos Árabes Unidos