Abstract
Levodopa is the most efficacious drug treatment option for Parkinson’s disease. However, in particular, high levodopa dosing may contribute to disease progression. Chronic levodopa metabolism reduces the methylation capacity and the antioxidant defense. Thus, this levodopa-induced free radical production complements the disease process, which considerably depends on free radical-induced, apoptotic neuronal cell death. Accordingly, clinical long-term studies with in the laboratory neuroprotective compounds failed in clinical investigations, as these studies were performed in levodopa-naive patients with Parkinson’s disease over a relative short interval. Therefore, the likelihood for a positive outcome was rather low, since trials only focused on the disease process in levodopa-naive patients. However, studies on antioxidant therapeutic strategies were positive in levodopa-treated Parkinson’s disease patients. To counteract these metabolic long-term levodopa-associated effects, chronic levodopa therapy should be combined with supplemental application of free radical scavengers and methyl group donating vitamins.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.