Levodopa, placebo and rotigotine change biomarker levels for oxidative stress

被引:4
作者
Muhlack, Siegfried [1 ]
Kinkel, Manuel [1 ]
Herrman, Lennard [1 ]
Mueller, Thomas [2 ]
机构
[1] Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, Bochum, Germany
[2] St Joseph Hosp Berlin Weissensee, Dept Neurol, Berlin, Germany
关键词
Homocysteine; cysteinylglycine; levodopa; placebo; rotigotine; oxidative stress; Parkinson's disease; PARKINSONS-DISEASE; ENDOTHELIAL DYSFUNCTION; THERAPY; NEURODEGENERATION; HOMOCYSTEINE; RECEPTORS; CYSTEINE;
D O I
10.1080/01616412.2017.1295520
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Introduction: Homocysteine increase and glutathione derivative cysteinyl-glycine fall are indirect biomarkers for oxidative stress, for instance due to dopamine D-1 receptor stimulation. Objectives: To investigate the influence of the D-1 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.
引用
收藏
页码:381 / 386
页数:6
相关论文
共 14 条
[1]  
Cadet JL, 2010, CNS NEUROL DISORD-DR, V9, P526
[2]   Absorption, Disposition, Metabolic Fate, and Elimination of the Dopamine Agonist Rotigotine in Man: Administration by Intravenous Infusion or Transdermal Delivery [J].
Cawello, Willi ;
Braun, Marina ;
Boekens, Hilmar .
DRUG METABOLISM AND DISPOSITION, 2009, 37 (10) :2055-2060
[3]   Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects [J].
Chambers, JC ;
Obeid, OA ;
Kooner, JS .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (12) :2922-2927
[4]  
Dorszewska J, 2007, ACTA NEUROBIOL EXP, V67, P113, DOI 10.55782/ane-2007-1639
[5]   Molecular Effects of L-dopa Therapy in Parkinson's Disease [J].
Dorszewska, Jolanta ;
Prendecki, Michal ;
Lianeri, Margarita ;
Kozubski, Wojciech .
CURRENT GENOMICS, 2014, 15 (01) :11-17
[6]  
Dorszewska J, 2013, CURR GENOMICS, V14, P518, DOI 10.2174/1389202914666131210210241
[7]   An Update on Pharmacological, Pharmacokinetic Properties and Drug-Drug Interactions of Rotigotine Transdermal System in Parkinson's Disease and Restless Legs Syndrome [J].
Elshoff, Jan-Peer ;
Cawello, Willi ;
Andreas, Jens-Otto ;
Mathy, Francois-Xavier ;
Braun, Marina .
DRUGS, 2015, 75 (05) :487-501
[8]  
Gupta Himanshu, 2013, Recent Pat Drug Deliv Formul, V7, P184
[9]   Levodopa-related cysteinyl-glycine and cysteine reduction with and without catechol-O-methyltransferase inhibition in Parkinson's disease patients [J].
Mueller, Thomas ;
Muhlack, Siegfried .
JOURNAL OF NEURAL TRANSMISSION, 2014, 121 (06) :643-648
[10]  
Müller T, 2013, EXPERT REV NEUROTHER, V13, P707, DOI [10.1586/ern.13.50, 10.1586/ERN.13.50]