ABT-089 and ABT-894 Reduce L-Dopa-Induced Dyskinesias in a Monkey Model of Parkinson’s Disease
Identifieur interne : 003F12 ( Ncbi/Merge ); précédent : 003F11; suivant : 003F13ABT-089 and ABT-894 Reduce L-Dopa-Induced Dyskinesias in a Monkey Model of Parkinson’s Disease
Auteurs : Danhui Zhang [États-Unis] ; Tanuja Bordia [États-Unis] ; Matthew Mcgregor [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 [ 0885-3185 ] ; 2014.
English descriptors
- KwdEn :
- Animals, Antiparkinson Agents (adverse effects), Antiparkinson Agents (therapeutic use), Dyskinesia, Drug-Induced (drug therapy), Female, Levodopa (adverse effects), Levodopa (therapeutic use), MPTP Poisoning (drug therapy), Male, Nicotinic Agonists (therapeutic use), Pyridines (therapeutic use), Pyrrolidines (therapeutic use), Saimiri, Treatment Outcome.
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa, Nicotinic Agonists, Pyridines, Pyrrolidines.
- drug therapy : Dyskinesia, Drug-Induced, MPTP Poisoning.
- Animals, Female, Male, Saimiri, Treatment Outcome.
Abstract
L-dopa-induced dyskinesias (LIDs) are a serious complication of L-dopa therapy for Parkinson’s disease for which there is little treatment. Accumulating evidence shows that nicotine and nicotinic acetylcholine receptor (nAChR) drugs decrease LIDs in parkinsonian animals. Here we examined the effect of two β2 nAChR agonists, ABT-089 and ABT-894, previously approved for phase 2 clinical trials for other indications.
Two sets of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys were administered L-dopa/carbidopa (10/2.5 mg/kg) twice daily 5 days/week until stably dyskinetic. Each set had a vehicle-treated, a nAChR agonist-treated and a nicotine-treated group, as a positive control. Set A monkeys had previously received other nAChR drugs (nAChR drug-primed), while Set B monkeys were initially nAChR drug-naïve.
Both sets were administered the partial agonist ABT-089 (0.01-1.0 mg/kg) orally 5 d/week twice daily 30 min before L-dopa with each dose given for 1-5 weeks. ABT-089 decreased LIDs 30-50% compared to vehicle-treated monkeys. Nicotine reduced LIDs by 70% in a parallel group. After 4 weeks washout, the effect of the full agonist ABT-894 (0.0001-0.10 mg/kg) was assessed on LIDs in Set A and Set B. ABT-894 reduced LIDs 70%, similar to nicotine. Both drugs acted equally well at α4β2* and α6β2* nAChRs; however, ABT-089 was 30-60 times less potent than ABT-894. Tolerance did not develop for the time periods tested (3-4 months). NAChR drugs did not worsen parkinsonism or cognitive ability. Emesis, a common problem with nAChR drugs, was not observed.
ABT-894 and ABT-089 appear good candidate nAChR drugs for the management of LIDs in Parkinson’s disease.
Url:
DOI: 10.1002/mds.25817
PubMed: 24515328
PubMed Central: 3990279
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000387
- to stream Pmc, to step Curation: 000387
- to stream Pmc, to step Checkpoint: 000052
- to stream PubMed, to step Corpus: 000585
- to stream PubMed, to step Curation: 000585
- to stream PubMed, to step Checkpoint: 000697
Links to Exploration step
PMC:3990279Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">ABT-089 and ABT-894 Reduce L-Dopa-Induced Dyskinesias in a Monkey Model of Parkinson’s Disease</title>
<author><name sortKey="Zhang, Danhui" sort="Zhang, Danhui" uniqKey="Zhang D" first="Danhui" last="Zhang">Danhui Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bordia, Tanuja" sort="Bordia, Tanuja" uniqKey="Bordia T" first="Tanuja" last="Bordia">Tanuja Bordia</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgregor, Matthew" sort="Mcgregor, Matthew" uniqKey="Mcgregor M" first="Matthew" last="Mcgregor">Matthew Mcgregor</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcintosh, J Michael" sort="Mcintosh, J Michael" uniqKey="Mcintosh J" first="J. Michael" last="Mcintosh">J. Michael Mcintosh</name>
<affiliation wicri:level="2"><nlm:aff id="A2">George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148 and Departments of Psychiatry and Biology, University of Utah, Salt Lake City, UT 84112</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Utah</region>
</placeName>
<wicri:cityArea>George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148 and Departments of Psychiatry and Biology, University of Utah, Salt Lake City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Decker, Michael W" sort="Decker, Michael W" uniqKey="Decker M" first="Michael W." last="Decker">Michael W. Decker</name>
<affiliation wicri:level="2"><nlm:aff id="A3">AbbVie, Inc, 1 North Waukegan Road, North Chicago, IL 60064-6125</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Illinois</region>
</placeName>
<wicri:cityArea>AbbVie, Inc, 1 North Waukegan Road, North Chicago</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24515328</idno>
<idno type="pmc">3990279</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990279</idno>
<idno type="RBID">PMC:3990279</idno>
<idno type="doi">10.1002/mds.25817</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000387</idno>
<idno type="wicri:Area/Pmc/Curation">000387</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000052</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">000585</idno>
<idno type="wicri:Area/PubMed/Curation">000585</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000697</idno>
<idno type="wicri:Area/Ncbi/Merge">003F12</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">ABT-089 and ABT-894 Reduce L-Dopa-Induced Dyskinesias in a Monkey Model of Parkinson’s Disease</title>
<author><name sortKey="Zhang, Danhui" sort="Zhang, Danhui" uniqKey="Zhang D" first="Danhui" last="Zhang">Danhui Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bordia, Tanuja" sort="Bordia, Tanuja" uniqKey="Bordia T" first="Tanuja" last="Bordia">Tanuja Bordia</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgregor, Matthew" sort="Mcgregor, Matthew" uniqKey="Mcgregor M" first="Matthew" last="Mcgregor">Matthew Mcgregor</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcintosh, J Michael" sort="Mcintosh, J Michael" uniqKey="Mcintosh J" first="J. Michael" last="Mcintosh">J. Michael Mcintosh</name>
<affiliation wicri:level="2"><nlm:aff id="A2">George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148 and Departments of Psychiatry and Biology, University of Utah, Salt Lake City, UT 84112</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Utah</region>
</placeName>
<wicri:cityArea>George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148 and Departments of Psychiatry and Biology, University of Utah, Salt Lake City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Decker, Michael W" sort="Decker, Michael W" uniqKey="Decker M" first="Michael W." last="Decker">Michael W. Decker</name>
<affiliation wicri:level="2"><nlm:aff id="A3">AbbVie, Inc, 1 North Waukegan Road, North Chicago, IL 60064-6125</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Illinois</region>
</placeName>
<wicri:cityArea>AbbVie, Inc, 1 North Waukegan Road, North Chicago</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antiparkinson Agents (adverse effects)</term>
<term>Antiparkinson Agents (therapeutic use)</term>
<term>Dyskinesia, Drug-Induced (drug therapy)</term>
<term>Female</term>
<term>Levodopa (adverse effects)</term>
<term>Levodopa (therapeutic use)</term>
<term>MPTP Poisoning (drug therapy)</term>
<term>Male</term>
<term>Nicotinic Agonists (therapeutic use)</term>
<term>Pyridines (therapeutic use)</term>
<term>Pyrrolidines (therapeutic use)</term>
<term>Saimiri</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term>
<term>Levodopa</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term>
<term>Levodopa</term>
<term>Nicotinic Agonists</term>
<term>Pyridines</term>
<term>Pyrrolidines</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term>
<term>MPTP Poisoning</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Female</term>
<term>Male</term>
<term>Saimiri</term>
<term>Treatment Outcome</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">L-dopa-induced dyskinesias (LIDs) are a serious complication of L-dopa therapy for Parkinson’s disease for which there is little treatment. Accumulating evidence shows that nicotine and nicotinic acetylcholine receptor (nAChR) drugs decrease LIDs in parkinsonian animals. Here we examined the effect of two β2 nAChR agonists, ABT-089 and ABT-894, previously approved for phase 2 clinical trials for other indications.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">Two sets of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys were administered L-dopa/carbidopa (10/2.5 mg/kg) twice daily 5 days/week until stably dyskinetic. Each set had a vehicle-treated, a nAChR agonist-treated and a nicotine-treated group, as a positive control. Set A monkeys had previously received other nAChR drugs (nAChR drug-primed), while Set B monkeys were initially nAChR drug-naïve.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Both sets were administered the partial agonist ABT-089 (0.01-1.0 mg/kg) orally 5 d/week twice daily 30 min before L-dopa with each dose given for 1-5 weeks. ABT-089 decreased LIDs 30-50% compared to vehicle-treated monkeys. Nicotine reduced LIDs by 70% in a parallel group. After 4 weeks washout, the effect of the full agonist ABT-894 (0.0001-0.10 mg/kg) was assessed on LIDs in Set A and Set B. ABT-894 reduced LIDs 70%, similar to nicotine. Both drugs acted equally well at α4β2* and α6β2* nAChRs; however, ABT-089 was 30-60 times less potent than ABT-894. Tolerance did not develop for the time periods tested (3-4 months). NAChR drugs did not worsen parkinsonism or cognitive ability. Emesis, a common problem with nAChR drugs, was not observed.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">ABT-894 and ABT-089 appear good candidate nAChR drugs for the management of LIDs in Parkinson’s disease.</p>
</sec>
</div>
</front>
</TEI>
<double pmid="24515328"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">ABT-089 and ABT-894 Reduce L-Dopa-Induced Dyskinesias in a Monkey Model of Parkinson’s Disease</title>
<author><name sortKey="Zhang, Danhui" sort="Zhang, Danhui" uniqKey="Zhang D" first="Danhui" last="Zhang">Danhui Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bordia, Tanuja" sort="Bordia, Tanuja" uniqKey="Bordia T" first="Tanuja" last="Bordia">Tanuja Bordia</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgregor, Matthew" sort="Mcgregor, Matthew" uniqKey="Mcgregor M" first="Matthew" last="Mcgregor">Matthew Mcgregor</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcintosh, J Michael" sort="Mcintosh, J Michael" uniqKey="Mcintosh J" first="J. Michael" last="Mcintosh">J. Michael Mcintosh</name>
<affiliation wicri:level="2"><nlm:aff id="A2">George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148 and Departments of Psychiatry and Biology, University of Utah, Salt Lake City, UT 84112</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Utah</region>
</placeName>
<wicri:cityArea>George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148 and Departments of Psychiatry and Biology, University of Utah, Salt Lake City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Decker, Michael W" sort="Decker, Michael W" uniqKey="Decker M" first="Michael W." last="Decker">Michael W. Decker</name>
<affiliation wicri:level="2"><nlm:aff id="A3">AbbVie, Inc, 1 North Waukegan Road, North Chicago, IL 60064-6125</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Illinois</region>
</placeName>
<wicri:cityArea>AbbVie, Inc, 1 North Waukegan Road, North Chicago</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24515328</idno>
<idno type="pmc">3990279</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990279</idno>
<idno type="RBID">PMC:3990279</idno>
<idno type="doi">10.1002/mds.25817</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000387</idno>
<idno type="wicri:Area/Pmc/Curation">000387</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000052</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">ABT-089 and ABT-894 Reduce L-Dopa-Induced Dyskinesias in a Monkey Model of Parkinson’s Disease</title>
<author><name sortKey="Zhang, Danhui" sort="Zhang, Danhui" uniqKey="Zhang D" first="Danhui" last="Zhang">Danhui Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bordia, Tanuja" sort="Bordia, Tanuja" uniqKey="Bordia T" first="Tanuja" last="Bordia">Tanuja Bordia</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcgregor, Matthew" sort="Mcgregor, Matthew" uniqKey="Mcgregor M" first="Matthew" last="Mcgregor">Matthew Mcgregor</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mcintosh, J Michael" sort="Mcintosh, J Michael" uniqKey="Mcintosh J" first="J. Michael" last="Mcintosh">J. Michael Mcintosh</name>
<affiliation wicri:level="2"><nlm:aff id="A2">George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148 and Departments of Psychiatry and Biology, University of Utah, Salt Lake City, UT 84112</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Utah</region>
</placeName>
<wicri:cityArea>George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148 and Departments of Psychiatry and Biology, University of Utah, Salt Lake City</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Decker, Michael W" sort="Decker, Michael W" uniqKey="Decker M" first="Michael W." last="Decker">Michael W. Decker</name>
<affiliation wicri:level="2"><nlm:aff id="A3">AbbVie, Inc, 1 North Waukegan Road, North Chicago, IL 60064-6125</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Illinois</region>
</placeName>
<wicri:cityArea>AbbVie, Inc, 1 North Waukegan Road, North Chicago</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA, 94025; USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="ISSN">0885-3185</idno>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">L-dopa-induced dyskinesias (LIDs) are a serious complication of L-dopa therapy for Parkinson’s disease for which there is little treatment. Accumulating evidence shows that nicotine and nicotinic acetylcholine receptor (nAChR) drugs decrease LIDs in parkinsonian animals. Here we examined the effect of two β2 nAChR agonists, ABT-089 and ABT-894, previously approved for phase 2 clinical trials for other indications.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">Two sets of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys were administered L-dopa/carbidopa (10/2.5 mg/kg) twice daily 5 days/week until stably dyskinetic. Each set had a vehicle-treated, a nAChR agonist-treated and a nicotine-treated group, as a positive control. Set A monkeys had previously received other nAChR drugs (nAChR drug-primed), while Set B monkeys were initially nAChR drug-naïve.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Both sets were administered the partial agonist ABT-089 (0.01-1.0 mg/kg) orally 5 d/week twice daily 30 min before L-dopa with each dose given for 1-5 weeks. ABT-089 decreased LIDs 30-50% compared to vehicle-treated monkeys. Nicotine reduced LIDs by 70% in a parallel group. After 4 weeks washout, the effect of the full agonist ABT-894 (0.0001-0.10 mg/kg) was assessed on LIDs in Set A and Set B. ABT-894 reduced LIDs 70%, similar to nicotine. Both drugs acted equally well at α4β2* and α6β2* nAChRs; however, ABT-089 was 30-60 times less potent than ABT-894. Tolerance did not develop for the time periods tested (3-4 months). NAChR drugs did not worsen parkinsonism or cognitive ability. Emesis, a common problem with nAChR drugs, was not observed.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">ABT-894 and ABT-089 appear good candidate nAChR drugs for the management of LIDs in Parkinson’s disease.</p>
</sec>
</div>
</front>
</TEI>
</pmc>
<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">ABT-089 and ABT-894 reduce levodopa-induced dyskinesias in a monkey model of Parkinson's disease.</title>
<author><name sortKey="Zhang, Danhui" sort="Zhang, Danhui" uniqKey="Zhang D" first="Danhui" last="Zhang">Danhui Zhang</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Health Sciences, SRI International, Menlo Park, California, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, Menlo Park, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bordia, Tanuja" sort="Bordia, Tanuja" uniqKey="Bordia T" first="Tanuja" last="Bordia">Tanuja Bordia</name>
</author>
<author><name sortKey="Mcgregor, Matthew" sort="Mcgregor, Matthew" uniqKey="Mcgregor M" first="Matthew" last="Mcgregor">Matthew Mcgregor</name>
</author>
<author><name sortKey="Mcintosh, J Michael" sort="Mcintosh, J Michael" uniqKey="Mcintosh J" first="J Michael" last="Mcintosh">J Michael Mcintosh</name>
</author>
<author><name sortKey="Decker, Michael W" sort="Decker, Michael W" uniqKey="Decker M" first="Michael W" last="Decker">Michael W. Decker</name>
</author>
<author><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2014">2014</date>
<idno type="RBID">pubmed:24515328</idno>
<idno type="pmid">24515328</idno>
<idno type="doi">10.1002/mds.25817</idno>
<idno type="wicri:Area/PubMed/Corpus">000585</idno>
<idno type="wicri:Area/PubMed/Curation">000585</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000697</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">ABT-089 and ABT-894 reduce levodopa-induced dyskinesias in a monkey model of Parkinson's disease.</title>
<author><name sortKey="Zhang, Danhui" sort="Zhang, Danhui" uniqKey="Zhang D" first="Danhui" last="Zhang">Danhui Zhang</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Health Sciences, SRI International, Menlo Park, California, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Health Sciences, SRI International, Menlo Park, California</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bordia, Tanuja" sort="Bordia, Tanuja" uniqKey="Bordia T" first="Tanuja" last="Bordia">Tanuja Bordia</name>
</author>
<author><name sortKey="Mcgregor, Matthew" sort="Mcgregor, Matthew" uniqKey="Mcgregor M" first="Matthew" last="Mcgregor">Matthew Mcgregor</name>
</author>
<author><name sortKey="Mcintosh, J Michael" sort="Mcintosh, J Michael" uniqKey="Mcintosh J" first="J Michael" last="Mcintosh">J Michael Mcintosh</name>
</author>
<author><name sortKey="Decker, Michael W" sort="Decker, Michael W" uniqKey="Decker M" first="Michael W" last="Decker">Michael W. Decker</name>
</author>
<author><name sortKey="Quik, Maryka" sort="Quik, Maryka" uniqKey="Quik M" first="Maryka" last="Quik">Maryka Quik</name>
</author>
</analytic>
<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
<idno type="eISSN">1531-8257</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antiparkinson Agents (adverse effects)</term>
<term>Antiparkinson Agents (therapeutic use)</term>
<term>Dyskinesia, Drug-Induced (drug therapy)</term>
<term>Female</term>
<term>Levodopa (adverse effects)</term>
<term>Levodopa (therapeutic use)</term>
<term>MPTP Poisoning (drug therapy)</term>
<term>Male</term>
<term>Nicotinic Agonists (therapeutic use)</term>
<term>Pyridines (therapeutic use)</term>
<term>Pyrrolidines (therapeutic use)</term>
<term>Saimiri</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term>
<term>Levodopa</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term>
<term>Levodopa</term>
<term>Nicotinic Agonists</term>
<term>Pyridines</term>
<term>Pyrrolidines</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term>
<term>MPTP Poisoning</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Female</term>
<term>Male</term>
<term>Saimiri</term>
<term>Treatment Outcome</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Levodopa-induced dyskinesias (LIDs) are a serious complication of levodopa therapy for Parkinson's disease for which there is little treatment. Accumulating evidence shows that nicotinic acetylcholine receptor (nAChR) drugs decrease LIDs in parkinsonian animals. Here, we examined the effect of two β2 nAChR agonists, ABT-089 and ABT-894, that previously were approved for phase 2 clinical trials for other indications. Two sets of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys were administered levodopa/carbidopa (10 mg/kg and 2.5 mg/kg, respectively) twice daily 5 days a week until they were stably dyskinetic. Each set had a vehicle-treated group, an nAChR agonist-treated group, and a nicotine-treated group as a positive control. Set A monkeys had previously received other nAChR drugs (nAChR drug-primed), whereas Set B monkeys were initially nAChR drug-naive. Both sets were administered the partial agonist ABT-089 (range, 0.01-1.0 mg/kg) orally 5 days a week twice daily 30 minutes before levodopa with each dose given for 1 to 5 weeks. ABT-089 decreased LIDs by 30% to 50% compared with vehicle-treated monkeys. Nicotine reduced LIDs by 70% in a parallel group. After 4 weeks of washout, the effect of the full agonist ABT-894 (range, 0.0001-0.10 mg/kg) was assessed on LIDs in Set A and Set B. ABT-894 reduced LIDs by 70%, similar to nicotine. Both drugs acted equally well at α4β2* and α6β2* nAChRs; however, ABT-089 was 30 to 60 times less potent than ABT-894. Tolerance did not develop for the time periods tested (range, 3-4 months). The nAChR drugs did not worsen parkinsonism or cognitive ability. Emesis, a common problem with nAChR drugs, was not observed. ABT-894 and ABT-089 appear to be good candidate nAChR drugs for the management of LIDs in Parkinson's disease.</div>
</front>
</TEI>
</pubmed>
</double>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003F12 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 003F12 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Santé |area= MovDisordV3 |flux= Ncbi |étape= Merge |type= RBID |clé= PMC:3990279 |texte= ABT-089 and ABT-894 Reduce L-Dopa-Induced Dyskinesias in a Monkey Model of Parkinson’s Disease }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:24515328" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \ | NlmPubMed2Wicri -a MovDisordV3
This area was generated with Dilib version V0.6.23. |