L-Dopa Prodrugs: An Overview of Trends for Improving Parkinsons 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.

Salvianolic Acid B Attenuates Toxin-Induced Neuronal Damage via Nrf2-Dependent Glial Cells-Mediated Protective Activity in Parkinson’s Disease Models

“…To date, clinical treatments are relied, in most cases, on the elevation of dopamine levels by the use of L-DOPA, its precursor or activating dopaminergic receptors via specific agonists, such as the ergot alkaloid derivatives. All of these drugs fail to prevent the progression of the degenerative process, and are limited by a progressive decrease in drug response, motor fluctuations, dyskinesias and drug-induced toxicity [27]–[29]. Thus, a new focus has shifted onto alternative therapeutic approaches that could provide an independent therapy or offer neuroprotective support to the existing drugs.…”

Optimization of a Small Tropomyosin-Related Kinase B (TrkB) Agonist 7,8-Dihydroxyflavone Active in Mouse Models of Depression

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