MovDisordV3, Main, Exploration, bibRecord, 000885

Nicotine reduces established L-dopa-induced dyskinesias in a monkey model of Parkinson’s disease

Identifieur interne : 000885 ( Main/Exploration ); précédent : 000884; suivant : 000886

Nicotine reduces established L-dopa-induced dyskinesias in a monkey model of Parkinson’s disease

Auteurs : Maryka Quik ; Archana Mallela ; Jason Ly ; Danhui Zhang

Source :

Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2013.

RBID : PMC:3787977

English descriptors

KwdEn :
- Animals, Anti-Dyskinesia Agents, Antiparkinson Agents, Cotinine (blood), Data Interpretation, Statistical, Dyskinesia, Drug-Induced (drug therapy), Female, Levodopa, MPTP Poisoning (drug therapy), Male, Nicotine (therapeutic use), Nicotinic Agonists (therapeutic use), Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (drug therapy), Saimiri.
MESH :
- chemical , blood : Cotinine.
- chemical , therapeutic use : Nicotine, Nicotinic Agonists.
- chemical : Anti-Dyskinesia Agents, Antiparkinson Agents, Levodopa.
- chemically induced : Parkinson Disease, Secondary.
- drug therapy : Dyskinesia, Drug-Induced, MPTP Poisoning, Parkinson Disease, Secondary.
- Animals, Data Interpretation, Statistical, Female, Male, Saimiri.

Abstract

Background

Although 3,4-dihydroxyphenylalanine (L-dopa) is the gold-standard treatment for Parkinson’s disease, it can lead to disabling dyskinesias. Previous work showed that nicotine reduces L-dopa-induced dyskinesias (LIDs) in several parkinsonian animal models. The goal of this study was to determine if the time of nicotine administration affected its ability to reduce LIDs in L-dopa-primed and L-dopa naïve monkeys, and also to test if tolerance developed to nicotine’s beneficial effects.

Methods

Monkeys were injected with MPTP (1.9–2.0 mg/kg sc) over 3–5 months until parkinsonian. Nicotine (300 μg/ml) was administered in drinking water (4–6 months) to L-dopa-primed or L-dopa-naïve monkeys, with L-dopa/carbidopa (10/2.5 mg/kg) gavaged twice daily.

Results

One set of MPTP-lesioned monkeys (n=23) was first gavaged with L-dopa and subsequently given nicotine 4 wk later when dyskinesias have plateaud or 8 wk later when dyskinesias are established. A 60–70% decrease in LIDs was observed after several weeks of nicotine treatment in both groups. A second set of monkeys (n=26) was given nicotine 8 or 2 weeks before L-dopa. In the 8 week nicotine pretreatment group, there was an immediate reduction in LIDs, which plateaud at 60–70%. In the 2 week nicotine pretreatment group, there were initial small decreases in LIDs, which plateaud at 60–70% several weeks later. Thus, nicotine pre- and post-treatment was similarly efficacious in reducing LIDs. The beneficial effect of nicotine persisted throughout the study (17–23 weeks). Nicotine did not worsen parkinsonism.

Conclusion

These data suggest that nicotine treatment has potential as a successful antidyskinetic therapy for Parkinson’s disease patients.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787977

DOI: 10.1002/mds.25594
PubMed: 23836409
PubMed Central: 3787977

Affiliations:

Le document en format XML

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<author><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name>
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<author><name sortKey="Ly, Jason" sort="Ly, Jason" uniqKey="Ly J" first="Jason" last="Ly">Jason Ly</name>
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<author><name sortKey="Mallela, Archana" sort="Mallela, Archana" uniqKey="Mallela A" first="Archana" last="Mallela">Archana Mallela</name>
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<author><name sortKey="Ly, Jason" sort="Ly, Jason" uniqKey="Ly J" first="Jason" last="Ly">Jason Ly</name>
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<author><name sortKey="Zhang, Danhui" sort="Zhang, Danhui" uniqKey="Zhang D" first="Danhui" last="Zhang">Danhui Zhang</name>
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<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<term>Data Interpretation, Statistical</term>
<term>Dyskinesia, Drug-Induced (drug therapy)</term>
<term>Female</term>
<term>Levodopa</term>
<term>MPTP Poisoning (drug therapy)</term>
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<term>Nicotine (therapeutic use)</term>
<term>Nicotinic Agonists (therapeutic use)</term>
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<term>Parkinson Disease, Secondary (drug therapy)</term>
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<term>Antiparkinson Agents</term>
<term>Levodopa</term>
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<term>MPTP Poisoning</term>
<term>Parkinson Disease, Secondary</term>
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<term>Data Interpretation, Statistical</term>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">Although 3,4-dihydroxyphenylalanine (L-dopa) is the gold-standard treatment for Parkinson’s disease, it can lead to disabling dyskinesias. Previous work showed that nicotine reduces L-dopa-induced dyskinesias (LIDs) in several parkinsonian animal models. The goal of this study was to determine if the time of nicotine administration affected its ability to reduce LIDs in L-dopa-primed and L-dopa naïve monkeys, and also to test if tolerance developed to nicotine’s beneficial effects.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">Monkeys were injected with MPTP (1.9–2.0 mg/kg sc) over 3–5 months until parkinsonian. Nicotine (300 μg/ml) was administered in drinking water (4–6 months) to L-dopa-primed or L-dopa-naïve monkeys, with L-dopa/carbidopa (10/2.5 mg/kg) gavaged twice daily.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">One set of MPTP-lesioned monkeys (n=23) was first gavaged with L-dopa and subsequently given nicotine 4 wk later when dyskinesias have plateaud or 8 wk later when dyskinesias are established. A 60–70% decrease in LIDs was observed after several weeks of nicotine treatment in both groups. A second set of monkeys (n=26) was given nicotine 8 or 2 weeks before L-dopa. In the 8 week nicotine pretreatment group, there was an immediate reduction in LIDs, which plateaud at 60–70%. In the 2 week nicotine pretreatment group, there were initial small decreases in LIDs, which plateaud at 60–70% several weeks later. Thus, nicotine pre- and post-treatment was similarly efficacious in reducing LIDs. The beneficial effect of nicotine persisted throughout the study (17–23 weeks). Nicotine did not worsen parkinsonism.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">These data suggest that nicotine treatment has potential as a successful antidyskinetic therapy for Parkinson’s disease patients.</p>
</sec>
</div>
</front>
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<tree><noCountry><name sortKey="Ly, Jason" sort="Ly, Jason" uniqKey="Ly J" first="Jason" last="Ly">Jason Ly</name>
<name sortKey="Mallela, Archana" sort="Mallela, Archana" uniqKey="Mallela A" first="Archana" last="Mallela">Archana Mallela</name>
<name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name>
<name sortKey="Zhang, Danhui" sort="Zhang, Danhui" uniqKey="Zhang D" first="Danhui" last="Zhang">Danhui Zhang</name>
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Movement Disorders (revue)

Nicotine reduces established L-dopa-induced dyskinesias in a monkey model of Parkinson’s disease

Nicotine reduces established L-dopa-induced dyskinesias in a monkey model of Parkinson’s disease

Source :

English descriptors

Abstract

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	Movement Disorders (revue)
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