Levodopa, placebo and rotigotine change biomarker levels for oxidative stress

Abstract

Introduction: Homocysteine increase and glutathione derivative cysteinyl-glycine fall are indirect biomarkers for oxidative stress, for instance due to dopamine D₁ receptor stimulation.

Objectives: To investigate the influence of the D₁ receptor agonists levodopa and rotigotine compared with placebo on homocysteine and cysteinyl-glycine in plasma of patients with Parkinson’s disease.

Methods: Patients received 100 mg levodopa, 4 mg rotigotine or placebo. Cysteinyl-glycine and homocysteine were measured every 30 min over three hours.

Results: Homocysteine rose during levodopa- and placebo administration. Rotigotine had no effect. Cysteine-glycine only increased after placebo- but not after levodopa- or rotigotine.

Discussion: Homocysteine elevation results from hepatic and gastrointestinal methylation processes. Transdermal rotigotine circumvents these methylation locations. Turnover of segregated alkyl residuals from rotigotine serves as methyl group donors, which counteract homocysteine increment. The placebo-related cysteinyl-glycine increase results from reduced free radical exposure. Low levodopa dosing and antioxidants in the rotigotine patch matrix prevented cysteinyl-glycine fall.

Keywords:

• Homocysteine
• cysteinyl-glycine
• levodopa
• placebo
• rotigotine
• oxidative stress
• Parkinson’s disease

Acknowledgements

We thank Barbara Kaminski, Tanja Steiner, Christine Stamm, Ulrike Beckmann, Marion Frickmann, Christa Kraushaar-Szesni for technical assistance. We thank the participating PD patients. We thank Willi Kohlhepp for scientific advice.