Does levodopa accelerate Parkinson's disease?

T. Simuni*, M. B. Stern

*Corresponding author for this work

Research output: Contribution to journalReview article

23 Scopus citations


Therapeutic options for the treatment of Parkinson's disease (PD) have expanded tremendously over the last 5 years, although levodopa remains the gold standard of therapy. A major therapeutic controversy has been the question of levodopa's potential to cause toxic effects on nigrostriatal cells, thus potentiating the progression of the disease. The answer to that question will guide physicians in the timing of levodopa initiation and its dosage. The issue of levodopa toxicity was initially raised because of its potential to cause long term adverse effects (dyskinesias and motor fluctuations), which are not observed in untreated patients. Levodopa-induced toxicity can be related to its potential to produce free radicals, which are known to be toxic to cells, in the process of its conversion to dopamine. In vitro data reveals some evidence of the toxic effect of levodopa although recent studies suggest that levodopa toxicity is dependent on its concentration and can be ameliorated in the presence of glial cells. In vivo data from healthy animals and humans does not convincingly demonstrate levodopa toxicity. There is no evidence of levodopa-induced neurotoxicity in patients with PD. Despite the absence of toxic effect in patients with PD, levodopa can cause long term complications like motor fluctuations and dyskinesias and should be used judiciously in the minimal clinically effective dose. In this article we review evidence for and against levodopa neurotoxicity and the implications of the 'levodopa controversy' on clinical practice.

Original languageEnglish (US)
Pages (from-to)399-408
Number of pages10
JournalDrugs and Aging
Issue number6
StatePublished - Jun 30 1999

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Does levodopa accelerate Parkinson's disease?'. Together they form a unique fingerprint.

  • Cite this