ArticleThe Journal of clinical investigation2020
Striatal Kir2 K+ channel inhibition mediates the antidyskinetic effects of amantadine.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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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.
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Who cites it
16 citing papers in PubMed, 38 citations in OpenAlex.
- A Phase 3, double-blind, placebo-controlled efficacy and safety study of ADS-5102 (Amantadine) extended-release capsules in people with multiple sclerosis and walking impairment.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Trial
- Neuromodulation to Promote Recovery Following Traumatic Brain Injury: A Narrative Review of Current Pharmacologic and Non-Pharmacologic Approaches.Brain sciences · 2026Review
- Article
- No New Relevant Treatment Options for L-DOPA-Induced Dyskinesia from a Clinician's Point of View.Neurology international · 2026Review
- Amantadine-based combination therapy of Parkinson's disease to prevent fluctuation and dyskinesia - experiences from a Parkinson outpatient clinic.Frontiers in aging neuroscience · 2026Article
- Levodopa Disrupts Activity Patterns and Encoding of Movement in Striatal Cholinergic Interneurons of Behaving Mice.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Neurophysiological Treatment Effects of Mesdopetam, Pimavanserin and Amantadine in a Rodent Model of Levodopa-Induced Dyskinesia.The European journal of neuroscience · 2025Article
- Levodopa-induced dyskinesia: interplay between the N-methyl-D-aspartic acid receptor and neuroinflammation.Frontiers in immunology · 2023Review
- Anticancer Activity of Amantadine and Evaluation of Its Interactions with Selected Cytostatics in Relation to Human Melanoma Cells.International journal of molecular sciences · 2022Article
- CalDAG-GEFI mediates striatal cholinergic modulation of dendritic excitability, synaptic plasticity and psychomotor behaviors.Neurobiology of disease · 2021Article
- Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.Journal of clinical medicine · 2021Review
- High-throughput characterization of photocrosslinker-bearing ion channel variants to map residues critical for function and pharmacology.PLoS biology · 2021Article
- Drug repurposing strategies of relevance for Parkinson's disease.Pharmacology research & perspectives · 2021Review
- Amantadine: reappraisal of the timeless diamond-target updates and novel therapeutic potentials.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Light-regulated voltage-gated potassium channels for acute interrogation of channel function in neurons and behavior.PloS one · 2021Article
- Contributive Role of TNF-α to L-DOPA-Induced Dyskinesia in a Unilateral 6-OHDA Lesion Model of Parkinson's Disease.Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Levodopa-induced dyskinesia (LID) poses a significant health care challenge for Parkinson's disease (PD) patients. Amantadine is currently the only drug proven to alleviate LID. Although its efficacy in treating LID is widely assumed to be mediated by blockade of N-methyl-D-aspartate (NMDA) glutamate receptors, our experiments demonstrate that at therapeutically relevant concentrations, amantadine preferentially blocks inward-rectifying K+ channel type 2 (Kir2) channels in striatal spiny projection neurons (SPNs) - not NMDA receptors. In so doing, amantadine enhances dendritic integration of excitatory synaptic potentials in SPNs and enhances - not antagonizes - the induction of long-term potentiation (LTP) at excitatory, axospinous synapses. Taken together, our studies suggest that the alleviation of LID in PD patients is mediated by diminishing the disparity in the excitability of direct- and indirect-pathway SPNs in the on state, rather than by disrupting LTP induction. This insight points to a pharmacological approach that could be used to effectively ameliorate LID and improve the quality of life for PD patients.
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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.