Trial reportThe Journal of clinical investigation2014
Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson's disease patients.
Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
- Cerebral serotonin transporter measurements with [Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Pooled it
- NLX-112 Randomized Phase 2A Trial: Safety, Tolerability, Anti-Dyskinetic, and Anti-Parkinsonian Efficacy.Movement disorders : official journal of the Movement Disorder Society · 2025Trial
- Efficacy of pramipexole combined with levodopa for Parkinson's disease treatment and their effects on QOL and serum TNF-The Journal of international medical research · 2020Trial
- Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson's disease: a dose-finding study.Brain : a journal of neurology · 2015Trial
- Emerging links between gut dysbiosis, aryl hydrocarbon receptor activation, and Parkinson's disease.Communications biology · 2026Review
- Targeting GPCR Signaling in Parkinson's Disease: From Molecular Pathology to Exercise-Based Therapeutics.Molecular neurobiology · 2026Review
- Pramipexole enhances levodopa's therapeutic efficacy in Parkinson's disease: Role of glutaredoxin-1 (GRX1), peroxiredoxin3 (PRX3), thioredoxin (TRX), 8-hydroxy-2 -deoxyguanosine (8-OHDG), and neurosteroid dehydroepiandrosterone sulfate (DHEA-S).Journal of medical biochemistry · 2026Article
- Effects of chemogenetic inhibition of serotonergic raphe-striatal neurons on L-DOPA-induced behaviors and neurochemistry in a rat model of Parkinson's disease.Acta neuropathologica communications · 2026Article
- Neuroimaging and Pathology Biomarkers in Parkinson's Disease and Parkinsonism.Brain sciences · 2026Article
- Onset of Motor Complications and Medication Dose in Newly Diagnosed and Treated Parkinson's Disease.Parkinson's disease · 2026Article
- Dynamic Changes in Midbrain-Striatal Association and Their Relationship With Levodopa-Induced Dyskinesia in Parkinson's Disease.Parkinson's disease · 2026Article
- Neuroimaging in advanced Parkinson's disease: insights into pathophysiology, biomarkers, and personalized therapies.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Levodopa treatment: impacts and mechanisms throughout Parkinson's disease progression.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Synaptic Interactions Between Serotonergic and Dopaminergic Systems in Parkinson's Disease.Current neuropharmacology · 2025Review
- Hemodynamic subtype profiling in tremor-dominant and akinetic-rigid Parkinson's disease using multi-delay pseudo-continuous arterial spin labeling imaging.Frontiers in human neuroscience · 2025Article
- The chronic use of serotonin norepinephrine reuptake inhibitors facilitates dyskinesia priming in early Parkinson's disease.Journal of neurology · 2024Article
- Serotonin as a biomarker of toxin-induced Parkinsonism.Molecular medicine (Cambridge, Mass.) · 2024Article
- The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson's disease.Frontiers in neural circuits · 2024Article
- Future Directions for Developing Non-dopaminergic Strategies for the Treatment of Parkinson's Disease.Current neuropharmacology · 2024Review
- Serotonergic Regulation of Synaptic Dopamine Levels Mitigates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.Journal of Parkinson's disease · 2024Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson's disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD.
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Registered trials
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.