ArticleThe Journal of pharmacology and experimental therapeutics2013
Nicotinic receptor agonists reduce L-DOPA-induced dyskinesias in a monkey model of Parkinson's disease.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Effect of nicotine on L-dopa-induced dyskinesia in animal models of Parkinson's disease: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Pooled it
- Levodopa treatment: impacts and mechanisms throughout Parkinson's disease progression.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- "Unraveling the role ofReceptors (Basel, Switzerland) · 2025Article
- Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson's Disease.Parkinson's disease · 2024Article
- Review
- Pathophysiological Mechanisms and Experimental Pharmacotherapy for L-Dopa-Induced Dyskinesia.Journal of experimental pharmacology · 2021Review
- Experimental Models of Cognitive Impairment for Use in Parkinson's Disease Research: The Distance Between Reality and Ideal.Frontiers in aging neuroscience · 2021Review
- Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson's Disease.Frontiers in neuroscience · 2021Review
- Targeting the cholinergic system in Parkinson's disease.Acta pharmacologica Sinica · 2020Review
- 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
- Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs.Nature reviews. Drug discovery · 2018Review
- The striatal cholinergic system in L-dopa-induced dyskinesias.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Review
- Preclinical Evidence for a Role of the Nicotinic Cholinergic System in Parkinson's Disease.Neuropsychology review · 2015Review
- α7 nicotinic receptor agonists reduce levodopa-induced dyskinesias with severe nigrostriatal damage.Movement disorders : official journal of the Movement Disorder Society · 2015Article
- Alpha7 nicotinic receptors as therapeutic targets for Parkinson's disease.Biochemical pharmacology · 2015Review
- Analysis of gait in rats with olivocerebellar lesions and ability of the nicotinic acetylcholine receptor agonist varenicline to attenuate impairments.Behavioural brain research · 2015Article
- In vitro and in vivo neuronal nicotinic receptor properties of (+)- and (-)-pyrido[3,4]homotropane [(+)- and (-)-PHT]: (+)-PHT is a potent and selective full agonist at α6β2 containing neuronal nicotinic acetylcholine receptors.ACS chemical neuroscience · 2015Article
- Evidence for a role for α6(∗) nAChRs in l-dopa-induced dyskinesias using Parkinsonian α6(∗) nAChR gain-of-function mice.Neuroscience · 2015Article
- Molecular imaging of levodopa-induced dyskinesias.Cellular and molecular life sciences : CMLS · 2015Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Abnormal involuntary movements or dyskinesias are a serious complication of long-term l-DOPA treatment of Parkinson's disease, for which there are few treatment options. Accumulating preclinical data show that nicotine decreases l-DOPA-induced dyskinesias (LIDs), suggesting that it may be a useful antidyskinetic therapy for Parkinson's disease. Here, we investigated whether nicotinic acetylcholine receptor (nAChR) agonists reduced LIDs in nonhuman primates. We first tested the nonselective nAChR agonist 1, 6,7,8,9-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine (varenicline), which offers the advantage that it is approved by the U.S. Food and Drug Administration for use in humans. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys (n = 23) were first administered l-DOPA/carbidopa (10/2.5 mg/kg) twice daily 5 days/week until stably dyskinetic. Oral varenicline (0.03-0.10 mg/kg) decreased LIDs ∼50% compared with vehicle-treated monkeys, whereas nicotine treatment (300 µg/ml in drinking water) reduced LIDs by 70% in a parallel group of animals. We next tested the selective α4β2*/α6β2* nAChR agonist TC-8831 [3-cyclopropylcarbonyl-3,6-diazabicyclo[3.1.1]heptane] on LIDs in the same set of monkeys after a 10-week washout. We also tested TC-8831 in another set of MPTP-lesioned monkeys (n = 16) that were nAChR drug-naïve. Oral TC-8831 (0.03-0.3 mg/kg) reduced LIDs in both sets by 30-50%. After a washout period, repeat TC-8831 dosing led to a greater decline in LIDs (60%) in both sets of monkeys that was similar to the effect of nicotine. Tolerance to any nAChR drug did not develop over the course of the study (3-4 months). NAChR drug treatment did not worsen parkinsonism or cognitive ability. These data suggest that nAChR agonists may be useful for the management of dyskinesias in l-DOPA-treated Parkinson's disease 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.