Journal of Neural Transmission

, Volume 121, Issue 6, pp 643–648

Levodopa-related cysteinyl–glycine and cysteine reduction with and without catechol-O-methyltransferase inhibition in Parkinson’s disease patients

Neurology and Preclinical Neurological Studies - Original Article


Oxidative stress is influenced by the thiol homeostasis, which regulates the redox milieu via glutathione. Components of glutathione metabolism are cysteine and cysteinyl–glycine. Both substrates decay following levodopa application or dopamine-related oxidative stress. Objective was to investigate the impact of an acute levodopa application with and without catechol-O-methyltransferase inhibitor on cysteine- and cysteinyl–glycine plasma levels. On two investigation days, 13 patients with Parkinson’s disease took one retarded release 200-mg levodopa/50 mg carbidopa-containing tablet or one 150-mg levodopa/50-mg carbidopa/200-mg entacapone formulation under standardized conditions. Levodopa, 3-O-methyldopa, cysteine and cysteinyl–glycine were measured at baseline, 80 and 140 min following levodopa administration. Cysteine and cysteinyl–glycine similarly decreased, levodopa was nearly equal during both conditions. Entacapone lowered 3-O-methyldopa. Cysteine decay may be due to an elevated glutathione generation, which consumes cysteine. Cysteinyl–glycine decrease results from the alternative glutathione transformation to its oxidized form glutathione dissulfide after free radical scavenging.


Cysteinyl–glycine Cysteine Oxidative stress Parkinson’s disease 


  1. Allen GF, Ullah Y, Hargreaves IP, Land JM, Heales SJ (2013) Dopamine but not l-dopa stimulates neural glutathione metabolism. Potential implications for Parkinson’s and other dopamine deficiency states. Neurochem Int 62:684–694PubMedCrossRefGoogle Scholar
  2. Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K (2004) Levodopa and the progression of Parkinson’s disease. N Engl J Med 351:2498–2508PubMedCrossRefGoogle Scholar
  3. Fujita Y, Izawa Y, Ali N, Kanematsu Y, Tsuchiya K, Hamano S, Tamaki T, Yoshizumi M (2006) Pramipexole protects against H2O2-induced PC12 cell death. Naunyn Schmiedebergs Arch Pharmacol 372:257–266PubMedCrossRefGoogle Scholar
  4. Inden M, Kitamura Y, Tamaki A, Yanagida T, Shibaike T, Yamamoto A, Takata K, Yasui H, Taira T, Ariga H, Taniguchi T (2009) Neuroprotective effect of the antiparkinsonian drug pramipexole against nigrostriatal dopaminergic degeneration in rotenone-treated mice. Neurochem Int 55:760–767PubMedCrossRefGoogle Scholar
  5. Jugel C, Ehlen F, Taskin B, Marzinzik F, Müller T, Klostermann F (2013) Neuropathy in Parkinson’s disease patients with intestinal levodopa infusion versus oral drugs. PLoS ONE 8:e66639PubMedCentralPubMedCrossRefGoogle Scholar
  6. Miklya I, Knoll B, Knoll J (2003) A pharmacological analysis elucidating why, in contrast to (−)-deprenyl (selegiline), alpha-tocopherol was ineffective in the DATATOP study. Life Sci 72:2641–2648PubMedCrossRefGoogle Scholar
  7. Miller JW, Shukitt-Hale B, Villalobos-Molina R, Nadeau MR, Selhub J, Joseph JA (1997) Effect of l-dopa and the catechol-O-methyltransferase inhibitor Ro 41-0960 on sulfur amino acid metabolites in rats. Clin Neuropharmacol 20:55–66PubMedCrossRefGoogle Scholar
  8. Müller T (2011) Motor complications, levodopa metabolism and progression of Parkinson’s disease. Expert Opin Drug Metab Toxicol 7:847–855PubMedCrossRefGoogle Scholar
  9. Müller T (2013) Detoxification and antioxidative therapy for levodopa-induced neurodegeneration in Parkinson’s disease. Expert Rev Neurother 13:707–718PubMedCrossRefGoogle Scholar
  10. Müller T, Kuhn W (2009) Cysteine elevation in levodopa-treated patients with Parkinson’s disease. Mov Disord 24:929–932PubMedCrossRefGoogle Scholar
  11. Müller T, Muhlack S (2011) Cysteinyl–glycine reduction as marker for levodopa-induced oxidative stress in Parkinson’s disease patients. Mov Disord 26:543–546PubMedCrossRefGoogle Scholar
  12. Müller T, Muhlack S (2012) Cysteine decrease following acute Levodopa intake in patients with Parkinson’s disease. Neurosci Lett 521(1):37–39PubMedCrossRefGoogle Scholar
  13. Müller T, Erdmann C, Bremen D, Schmidt WE, Muhlack S, Woitalla D, Goetze O (2006) Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients. Clin Neuropharmacol 29:61–67PubMedCrossRefGoogle Scholar
  14. Müller T, Ander L, Kolf K, Woitalla D, Muhlack S (2007) Comparison of 200 mg retarded release levodopa/carbidopa—with 150 mg levodopa/carbidopa/entacapone application: pharmacokinetics and efficacy in patients with Parkinson’s disease. J Neural Transm 114:1457–1462PubMedCrossRefGoogle Scholar
  15. Müller T, van Laar T, Cornblath DR, Odin P, Klostermann F, Grandas FJ, Ebersbach G, Urban PP, Valldeoriola F, Antonini A (2013) Peripheral neuropathy in Parkinson’s disease: levodopa exposure and implications for duodenal delivery. Parkinsonism Relat Disord 19:501–507PubMedCrossRefGoogle Scholar
  16. NINDS NET-PD Investigators (2007) A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology 68:20–28CrossRefGoogle Scholar
  17. Parkinson Study Group (2002) Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA 287:1653–1661CrossRefGoogle Scholar
  18. Przuntek H, Conrad B, Dichgans J, Kraus PH, Krauseneck P, Pergande G, Rinne U, Schimrigk K, Schnitker J, Vogel HP (1999) SELEDO: a 5-year long-term trial on the effect of selegiline in early Parkinsonian patients treated with levodopa. Eur J Neurol 6:141–150PubMedCrossRefGoogle Scholar
  19. Riederer P, Lachenmayer L, Laux G (2004) Clinical applications of MAO-inhibitors. Curr Med Chem 11:2033–2043PubMedCrossRefGoogle Scholar
  20. Riederer P, Gerlach M, Müller T, Reichmann H (2007) Relating mode of action to clinical practice: dopaminergic agents in Parkinson’s disease. Parkinsonism Relat Disord 13:466–479PubMedCrossRefGoogle Scholar
  21. Schapira AH, McDermott MP, Barone P, Comella CL, Albrecht S, Hsu HH, Massey DH, Mizuno Y, Poewe W, Rascol O, Marek K (2013) Pramipexole in patients with early Parkinson’s disease (PROUD): a randomised delayed-start trial. Lancet Neurol 12:747–755PubMedCentralPubMedCrossRefGoogle Scholar
  22. Shults CW (2005) Therapeutic role of coenzyme Q(10) in Parkinson’s disease. Pharmacol Ther 107:120–130PubMedCrossRefGoogle Scholar
  23. Smeyne M, Smeyne RJ (2013) Glutathione metabolism and Parkinson’s disease. Free Radic Biol Med 62:13–25PubMedCrossRefGoogle Scholar
  24. Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25:2649–2653PubMedCrossRefGoogle Scholar
  25. Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, Lang AE, Rascol O, Ribeiro MJ, Remy P, Poewe WH, Hauser RA, Brooks DJ (2003) Slower progression of Parkinson’s disease with ropinirole versus levodopa: the REAL-PET study. Ann Neurol 54:93–101PubMedCrossRefGoogle Scholar
  26. Zeevalk GD, Razmpour R, Bernard LP (2008) Glutathione and Parkinson’s disease: is this the elephant in the room? Biomed Pharmacother 62:236–249PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Department of NeurologySt. Joseph Hospital Berlin-WeissenseeBerlinGermany
  2. 2.Department of Neurology, St. Josef HospitalRuhr University BochumBochumGermany

Personalised recommendations