Evidence map›Paper›PMID 40214767›Full record

ReviewJournal of neural transmission (Vienna, Austria : 1996)2025

Levodopa treatment: impacts and mechanisms throughout Parkinson's disease progression.

Peter Riederer, Sabrina Strobel, Toshiharu Nagatsu, Hirohisa Watanabe, Xiqun Chen, Peter-Andreas Löschmann, Jeswinder Sian-Hulsmann, Wolfgang H Jost, Thomas Müller, Johannes M Dijkstra and 1 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of neural transmission (Vienna, Austria : 1996), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Observational
  4. Review
  5. Review
  6. On-demand therapies-emergency medication or daily routine?Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  7. Early clinical experience with IPX203 in Parkinson's disease with motor fluctuations.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  8. A Phase 1 Study of Convection-Enhanced Delivery of Intraputaminal AAV2-GDNF in Advanced Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Comparative pharmacovigilance of Levodopa and Pramipexole: a disproportionality analysis of the FAERS database.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  14. What's in a name? reframing advanced Parkinson's disease as a multidimensional state.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  15. Article
  16. Plant-derived therapies in Parkinson's disease: a systematic review of clinical evidence.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  17. Review
  18. Article
  19. Non-motor fluctuation patterns in dyskinetic patients with advanced Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Peter Riederer *Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, University of Wuerzburg, Würzburg, Germany.
Sabrina Strobel *Institute of Pathology, Julius-Maximilian-University of Wuerzburg, Würzburg, Germany.
Toshiharu NagatsuCenter for Research Promotion and Support, Fujita Health University, Toyoake, Aichi, Japan.
Hirohisa WatanabeDepartment of Neurology, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
Xiqun ChenMass. General Institute for Neurodegenerative Disease. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Peter-Andreas Löschmann, Am Hamburger Bahnhof 3, 10557, Berlin, Germany.
Jeswinder Sian-HulsmannDepartment of Human Anatomy and Medical Physiology, University of Nairobi, P.O. Box 30197, Nairobi, 00100, Kenya.
Wolfgang H JostParkinson-Klinik Ortenau, Wolfach, Germany.
Thomas MüllerDepartment of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstrasse 1, 13088, Berlin, Germany.
Johannes M DijkstraCenter for Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
Camelia-Maria MonoranuInstitute of Pathology, Department of Neuropathology, Julius-Maximilian-University Ofwuerzburg, Würzburg, Germany. camelia-maria.monoranu@uni-wuerzburg.de.ORCID 0000-0002-1345-7363

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treatment with levodopa, a precursor of dopamine (DA), to compensate for the loss of endogenous DA in Parkinson's disease (PD), has been a success story for over 50 years. However, in late stages of PD, the progressive degeneration of dopaminergic neurons and the ongoing reduction in endogenous DA concentrations make it increasingly difficult to maintain normal-like DA function. Typically, in late PD, higher doses of levodopa are required, and the fluctuations in striatal DA concentrations-reflecting the timing pattern of levodopa administrations-become more pronounced. These DA fluctuations can include highs that induce involuntary movements (levodopa-induced dyskinesia, LID) or lows that result in insufficient suppression of PD symptoms ("OFF" phases). The enhanced fluctuations primarily arise from the loss of DA buffering capacity, resulting from the degeneration of DA neurons, and an increased reliance on levodopa-derived DA release as a "false neurotransmitter" by serotonergic neurons. In many patients, the LID and OFF-phases can be alleviated by modifying the levodopa therapy to provide a more continuous delivery or by using additional medications, such as monoamine oxidase-B (MAO-B) inhibitors, amantadine, or dopaminergic receptor agonists. Understanding the challenges faced by levodopa therapy also requires considering that the PD striatum is characterized not only by the loss of DA neurons but also by neuroplastic adaptations and PD-induced degenerations of other neural populations. This review provides a broad overview on the use of levodopa in treating PD, with a focus on the underlying science of the challenges encountered in late stages of the disease.

Indexed as

Antiparkinson AgentsLevodopaParkinson DiseaseAnimalsDisease ProgressionHumansAntiparkinson AgentsLevodopaLevodopaLevodopa-induced dyskinesia (LID)Long duration response (LDR)Mode of actionOFF-phaseParkinson’s diseaseProgression

Identifiers

PMID40214767
PMCPMC12116664

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.