α7 nicotinic receptor agonists reduce levodopa-induced dyskinesias with severe nigrostriatal damage.
Identifieur interne : 000006 ( PubMed/Curation ); précédent : 000005; suivant : 000007α7 nicotinic receptor agonists reduce levodopa-induced dyskinesias with severe nigrostriatal damage.
Auteurs : Danhui Zhang [États-Unis] ; Matthew Mcgregor [États-Unis] ; Tanuja Bordia [États-Unis] ; Xiomara A. Perez [États-Unis] ; J Michael Mcintosh [États-Unis] ; Michael W. Decker [États-Unis] ; Maryka Quik [États-Unis]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2015.
Abstract
ABT-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.
DOI: 10.1002/mds.26453
PubMed: 26573698
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<front><div type="abstract" xml:lang="en">ABT-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.</div>
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<Month>11</Month>
<Day>17</Day>
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<Title>Movement disorders : official journal of the Movement Disorder Society</Title>
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<ArticleTitle>α7 nicotinic receptor agonists reduce levodopa-induced dyskinesias with severe nigrostriatal damage.</ArticleTitle>
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<Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">ABT-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.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">Monkeys (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.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">With 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.</AbstractText>
<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">The 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. © 2015 International Parkinson and Movement Disorder Society.</AbstractText>
<CopyrightInformation>© 2015 International Parkinson and Movement Disorder Society.</CopyrightInformation>
</Abstract>
<AuthorList><Author><LastName>Zhang</LastName>
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<Keyword MajorTopicYN="N">Parkinson's disease</Keyword>
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