Advertisement

Journal of Neural Transmission

, Volume 118, Issue 12, pp 1659–1660 | Cite as

Mechanisms underlying and medical management of l-Dopa-associated motor complications

  • Manfred Gerlach
  • Peter Riederer
  • Dieter Scheller
Editorial

Motor complications, particularly motor fluctuations such as wearing-off, on–off phenomena, and several different types of dyskinesia such as peak-dose, diphasic, wearing-off, chorea, dystonia and athetosis (collectively called dyskinesia) seem to be an inevitable consequence of l-Dopa (l-3,4-dihydroxyphenylalanine, levodopa) therapy of patients suffering from Parkinson’s Disease (Jankovic 2005; Müller and Russ 2006). However, not all patients develop dyskinesia even after long periods of treatment suggesting that specific deteriorations or adaptations occur in one group of patients but not in the other. The present understanding of the underlying mechanisms of those differences is far from being known. The stage of the illness (degree of dopaminergic degeneration and loss of nigro-striatal projections) as well as the dose and frequency of l-Dopa treatment have been considered as essential contributors to the induction and expression of the involuntary movements. Age of the patients...

References

  1. Boroojerdi B, Wolff HM, Braun M, Scheller DK (2010) Rotigotine transdermal patch for the treatment of Parkinson’s disease and restless legs syndrome. Drugs Today (Barc) 46(7):483–505CrossRefGoogle Scholar
  2. Chase TN (1998) The significance of continuous dopaminergic stimulation in the treatment of Parkinson’s disease. Drugs 55(S1):1–9PubMedCrossRefGoogle Scholar
  3. Dekundy A, Gravius A, Hechenberger M, Pietraszek M, Nagel J, Tober C, van der Elst M, Mela F, Parsons CG, Danysz W (2011). Pharmacological characterization of MRZ-8676, a novel negative allosteric modulator of subtype 5 metabotropic glutamate receptors (mGluR5): focus on l-DOPA-induced dyskinesia. J Neural Transm 118(12). doi: 10.1007/s00702-010-0526-0
  4. Gerlach M, Bartoszyk GD, Riederer P, Dean O, van den Buuse M (2011a) Role of dopamine D3 receptors and serotonin 5-HT1A receptors in levodopa-induced dyskinesias and effects of sarizotan in the 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. J Neural Transm 118(12). doi: 10.1007/s00702-010-0571-8
  5. Gerlach M, Beck J, Riederer P, van den Buuse M (2011b) Flibanserin attenuates l-DOPA-sensitized contraversive circling in the unilaterally 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. J Neural Transm 118(12). doi: 10.1007/s00702-010-0570-9
  6. Grünblatt E, Schmidt WJ, Scheller DKA, Riederer P, Gerlach M (2011) Transcriptional alterations under continuous or pulsatile dopaminergic treatment in dyskinetic rats. J Neural Transm 118(12). doi:  10.1007/s00702-010-0552-y
  7. Iravani MM, Jenner P (2011) Mechanisms underlying the onset and expression of levodopa induced dyskinesia and their pharmacological manipulation. J Neural Transm 118(12). doi: 10.1007/s00702-011-0698-2
  8. Jankovic JJ (2005) Motor fluctuations and dyskinesias in Parkinson’s disease: Clinical manifestations. Mov Disord 20(Suppl 11):S11–S16PubMedCrossRefGoogle Scholar
  9. Jenner P, McCreary AC, Scheller DKA (2011) Continuous drug delivery in early and late stage Parkinson’s disease as a strategy for avoiding dyskinesia induction and expression. J Neural Transm 118(12). doi: 10.1007/s00702-011-0703-9
  10. Müller T, Russ H (2006) Levodopa, motor fluctuations and dyskinesia in Parkinson’s disease. Expert Opin Pharmacol 7:1715–1730CrossRefGoogle Scholar
  11. Wolf E, Sepppi K, Katzenschlager R et al (2010) Long-term antidyskinetic efficacy of amantadine in Parkinson’s disease. Mov Disord 25:1357–1363PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Manfred Gerlach
    • 1
  • Peter Riederer
    • 2
  • Dieter Scheller
    • 3
  1. 1.Laboratory for Clinical Neurobiology, Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyUniversity of WürzburgWürzburgGermany
  2. 2.Laboratory for Clinical Neurochemistry, Department of Psychiatry, Psychosomatics and Psychotherapy, National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases ResearchUniversity of WürzburgWürzburgGermany
  3. 3.Department Pharmacology of Parkinson’s Disease and Movement DisordersCNS Research UCB Pharma S.ABraine l’AlleudBelgium

Personalised recommendations