Abstract
Parkinson’s disease is one of the most common progressive neurodegenerative disorder. It is characterized by the depletion of dopamine in the dopaminergic neurons of the striatum of the brain. Pharmacological treatment involves the administration of a dopamine precursor, levodo- pa (L-Dopa), which crosses the blood-brain barrier and replaces the loss of dopamine in the brain. One of the main drawbacks of the ad- ministration of L-Dopa is its short half-life, due to the presence of enzymes, such as the amino acid decarboxylase (AADC), able to rapidly me- tabolize L-Dopa. For this reason the intake of L-Dopa takes always place together with an AADC inhibitor such as carbidopa. The assumption of carbidopa increases L-Dopa half-life, but several patients need to increase the dosage of the pharmacological therapy during the progression of the disease. Another area of dispute is represented by the possibility that L-Dopa can exert a toxic effect on the cells, both in peripheral and in central nervous system, increasing the production of ROS following its conversion to dopamine. Past studies reported toxic effects of L-Dopa in vitro and show conflicting data in in vivo experiments. More recent studies have however shown that L-dopa may exert a protective and antioxidant effect on dopaminergic cells, and its combination with carbidopa in pharmacological treatment amplifies antioxidant capability.
Highlights
The first clinical features of Parkinson’s Disease (PD) were described and published by James Parkinson in 1817 [1]
Pharmacological treatment aims to slow down neurodegeneration replacing the loss of dopamine, but trial with oral dopamine failed because it cannot cross the blood-brain barrier
L-Dopa administration is usually associated with peripheral dopa decarboxylase (DDC) inhibitors to increase the amount of drug available to cross the blood brain barrier [9], the response duration to each dose shortens as the disease progresses [10]
Summary
The first clinical features of Parkinson’s Disease (PD) were described and published by James Parkinson in 1817 [1]. Following from this, George Cotzias demonstrated that high doses of dopamine’s prodrug, levodopa (L-Dopa) promptly enhanced clinical function in PD patients [4] and corrected the mechanical disorders at the early stage of the disease [2]. One of the problems of the treatment with L-Dopa alone is its low central nervous system (CNS) bioavailability because of rapid peripheral decarboxylation to dopamine [5,6]. Concomitant administration of a dopa decarboxylase (DDC) inhibitor, such as carbidopa, was later demonstrated to markedly increase L-Dopa CNS bioavailability [7,8]. L-Dopa administration is usually associated with peripheral DDC inhibitors to increase the amount of drug available to cross the blood brain barrier [9], the response duration to each dose shortens as the disease progresses [10]. The purpose of this review is to present the latest experimental evidences about the effects of L-Dopa and carbidopa treatments
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