Objective: The objective was 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.

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

Methods: 14 Patients were tested under three different conditions following an overnight fast and washout of their additional PD drug regime, which was initiated after the trial again on each day. They took either a 100 mg L-dopa/25 mg benserazide tablet (Madopar LT ®) in solution or a 4 mg rotigotine patch (Neupro®) or placebo (patch BSN medical Leukomed ®) under double blind, randomised conditions with prior light exposed 100 ml orange juice, dissolved in 100 ml water, on each investigation day. The orange juice containing drink should avoid possible disturbances of the blinding procedure as consequence of taste sensations and white discoloring resulting from the L-dopa/benserazide solution. All study participants received a standardised breakfast (300 kcal [bread roll, margarine, jam]) at 7.15 am and took 20 mg domperidon (Motilium ®) at 7.30 am, to prevent nausea during each condition. The PD patients received the corresponding medicine for the designed condition before the second blood sampling at 8 am. There was at least one day between each investigation day. Blood sampling was performed at moments -30 minutes, 0 before drug application and 30, 60, 90, 120, 150 minutes after drug intake. Cysteinyl-glycine and homocysteine were measured every 30 minutes over three hours.

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

Conclusions: Homocysteine elevation results from hepatic and gastrointestinal methylation processes. Transdermal rotigotine circumvents these methylation locations. Turnover of segregated alkyl residuals from rotigotine serve 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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levodopa-placebo-and-rotigotine-change-biomarker-levels-for-oxidative-stress/