ArticleMovement disorders : official journal of the Movement Disorder Society2015
α7 nicotinic receptor agonists reduce levodopa-induced dyskinesias with severe nigrostriatal damage.
Article in Movement disorders : official journal of the Movement Disorder Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- The Role of α7-Nicotinic Acetylcholine Receptors in the Pathophysiology and Treatment of Parkinson's Disease.International journal of molecular sciences · 2025Review
- Physiologic Functions and Therapeutic Applications of α7 Nicotinic Acetylcholine Receptor in Brain Disorders.Pharmaceutics · 2022Review
- Roles of the Functional Interaction between Brain Cholinergic and Dopaminergic Systems in the Pathogenesis and Treatment of Schizophrenia and Parkinson's Disease.International journal of molecular sciences · 2021Review
- Exposure to varenicline protects against locomotor alteration in a MPTP mouse model of Parkinson's disease.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
- Review
- Dystonia and levodopa-induced dyskinesias in Parkinson's disease: Is there a connection?Neurobiology of disease · 2019Review
- Receptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson's Disease.Biomolecules · 2019Review
- Critical Roles of Glutaredoxin in Brain Cells-Implications for Parkinson's Disease.Antioxidants & redox signaling · 2019Review
- Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Review
- The Rodent Models of Dyskinesia and Their Behavioral Assessment.Frontiers in neurology · 2019Review
- Dyskinesia and brain-derived neurotrophic factor levels after long-term levodopa and nicotinic receptor agonist treatments in female mice with near-total unilateral dopaminergic denervation.BMC neuroscience · 2018Article
- Proteomic Investigation of Murine Neuronal α7-Nicotinic Acetylcholine Receptor Interacting Proteins.Journal of proteome research · 2018Article
- The striatal cholinergic system in L-dopa-induced dyskinesias.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- The use of nonhuman primate models to understand processes in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- The current agonists and positive allosteric modulators ofActa pharmaceutica Sinica. B · 2017Review
- Preclinical Evidence for a Role of the Nicotinic Cholinergic System in Parkinson's Disease.Neuropsychology review · 2015Review
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Authors and funding
7 authors at 4 institutions in 1 country.
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Abstract
backgroundABT-126 is a novel, safe, and well-tolerated α7 nicotinic receptor agonist in a Phase 2 Alzheimer's disease study. We tested the antidyskinetic effect of ABT-126 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated squirrel monkeys with moderate and more severe nigrostriatal damage.
methodsMonkeys (n = 21, set 1) were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-2×. When parkinsonian, they were gavaged with levodopa (10 mg/kg)/carbidopa (2.5 mg/kg) twice daily and dyskinesias rated. They were then given nicotine in drinking water (n = 5), or treated with vehicle (n = 6) or ABT-126 (n = 10) twice daily orally 30 min before levodopa. Set 1 was then re-lesioned 1 to 2 times for a total of 3 to 4 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injections. The antidyskinetic effect of ABT-126, nicotine, and the β2* nicotinic receptor agonist ABT-894 was re-assessed. Another group of monkeys (n = 23, set 2) were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine only 1× to 2×. They were treated with levodopa/carbidopa, administered the α7 agonist ABT-107 (n = 6), ABT-894 (n = 6), nicotine (n = 5), or vehicle (n = 6) and dyskinesias evaluated. All monkeys were euthanized and the dopamine transporter measured.
resultsWith moderate nigrostriatal damage (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1×-2×), ABT-126 dose-dependently decreased dyskinesias (∼60%), with similar results seen with ABT-894 (∼60%) or nicotine (∼60%). With more severe damage (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 3-4×), ABT-126 and nicotine reduced dyskinesias, but ABT-894 did not. The dopamine transporter was 41% and 8.9% of control, with moderate and severe nigrostriatal damage, respectively. No drug modified parkinsonism.
conclusionThe novel α7 nicotinic receptor drug ABT-126 reduced dyskinesias in monkeys with both moderate and severe nigrostriatal damage. ABT-126 may be useful to reduce dyskinesias in both early- and later-stage Parkinson's disease.
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