Levodopa in Parkinson's disease: neurotoxicity issue laid to rest?

Abstract:

:Orally administered levodopa remains the most effective symptomatic treatment for Parkinson's disease. The introduction of levodopa therapy is often delayed, however, because of the fear that it might be toxic for the remaining dopaminergic neurons, and thus accelerate the deterioration of the patient's condition. Evidence for levodopa toxicity comes mainly from in vitro studies which have demonstrated that levodopa can damage dopaminergic neurons by a mechanism that probably involves oxidative stress. It is widely accepted, however, that levodopa is not toxic for healthy animals and humans who do not have Parkinson's disease. It has been argued that the lesioned mesostriatal dopaminergic system could be more vulnerable to levodopa-induced toxicity, because the brain extracellular concentrations attained by levodopa are higher when the dopaminergic system is damaged, and remaining dopaminergic neurons experience a process of compensatory hyperactivity. Evidence for in vivo levodopa toxicity in animal models of Parkinson's disease is scarce and contradictory. A comprehensive recent study failed to find any evidence of levodopa toxicity in rats with either moderate or severe lesions of the mesostriatal dopaminergic system. Concerning the hypothesis of toxicity, some recent reports have shown that levodopa can have trophic effects on dopaminergic neurons in vitro, and our own work has shown that long term levodopa therapy promotes recovery of striatal dopaminergic markers in rats with moderate nigrostriatal lesions. Given that neither epidemiological nor clinical studies have ever provided evidence to support that long term levodopa administration can accelerate the progression of Parkinson's disease, we believe that levodopa therapy should not be delayed on the basis of an unconfirmed hypothesis.

journal_name

Drug Saf

journal_title

Drug safety

authors

Murer MG,Raisman-Vozari R,Gershanik O

doi

10.2165/00002018-199921050-00001

keywords:

subject

Has Abstract

pub_date

1999-11-01 00:00:00

pages

339-52

issue

5

eissn

0114-5916

issn

1179-1942

journal_volume

21

pub_type

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