A trial of dextromethorphan in parkinsonian patients with motor response complications
Identifieur interne : 008005 ( Main/Merge ); précédent : 008004; suivant : 008006A trial of dextromethorphan in parkinsonian patients with motor response complications
Auteurs : Leo Verhagen Metman [États-Unis] ; Pierre J. Blanchet [États-Unis] ; Pep N Van Den Munckhof [États-Unis] ; Paolo Del Dotto [États-Unis] ; Remco Natté [États-Unis] ; Thomas N. Chase [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 1998-05.
English descriptors
- KwdEn :
- Activities of Daily Living (classification), Aged, Antiparkinson Agents (adverse effects), Antiparkinson Agents (therapeutic use), Carbidopa (adverse effects), Carbidopa (therapeutic use), Cross-Over Studies, Dextromethorphan (adverse effects), Dextromethorphan (therapeutic use), Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Dyskinesia, Drug-Induced (diagnosis), Dyskinesia, Drug-Induced (drug therapy), Female, Glutamate, Humans, Male, Middle Aged, Motor Skills (drug effects), Motor complications, N-Methylaspartate (antagonists & inhibitors), NMDA, Neurologic Examination (drug effects), Parkinson Disease (diagnosis), Parkinson Disease (drug therapy).
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Carbidopa, Dextromethorphan.
- chemical , antagonists & inhibitors : N-Methylaspartate.
- classification : Activities of Daily Living.
- diagnosis : Dyskinesia, Drug-Induced, Parkinson Disease.
- drug effects : Motor Skills, Neurologic Examination.
- drug therapy : Dyskinesia, Drug-Induced, Parkinson Disease.
- chemical , therapeutic use : Antiparkinson Agents, Carbidopa, Dextromethorphan.
- Aged, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged.
Abstract
The effects of the NMDA antagonist dextromethorphan (DM) on levodopa‐associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open‐label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60–120 mg/day). The 12 remaining patients either experinced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double‐blind, placebo‐controlled, crossover study with two 2‐week arms separted by 1 week wash‐out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% accfording to UPDRS interviews, without compromising the anti‐Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa‐associated motor complications.
Url:
DOI: 10.1002/mds.870130307
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Chase</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="1998-05">1998-05</date><biblScope unit="vol">13</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="414">414</biblScope><biblScope unit="page" to="417">417</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">6678D223545AE509A9A53066038F609551C223B3</idno><idno type="DOI">10.1002/mds.870130307</idno><idno type="ArticleID">MDS870130307</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Activities of Daily Living (classification)</term><term>Aged</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Carbidopa (adverse effects)</term><term>Carbidopa (therapeutic use)</term><term>Cross-Over Studies</term><term>Dextromethorphan (adverse effects)</term><term>Dextromethorphan (therapeutic use)</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Therapy, Combination</term><term>Dyskinesia, Drug-Induced (diagnosis)</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Female</term><term>Glutamate</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Motor Skills (drug effects)</term><term>Motor complications</term><term>N-Methylaspartate (antagonists & inhibitors)</term><term>NMDA</term><term>Neurologic Examination (drug effects)</term><term>Parkinson Disease (diagnosis)</term><term>Parkinson Disease (drug therapy)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Dextromethorphan</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>N-Methylaspartate</term></keywords><keywords scheme="MESH" qualifier="classification" xml:lang="en"><term>Activities of Daily Living</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Motor Skills</term><term>Neurologic Examination</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Dextromethorphan</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Cross-Over Studies</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The effects of the NMDA antagonist dextromethorphan (DM) on levodopa‐associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open‐label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60–120 mg/day). The 12 remaining patients either experinced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double‐blind, placebo‐controlled, crossover study with two 2‐week arms separted by 1 week wash‐out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% accfording to UPDRS interviews, without compromising the anti‐Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa‐associated motor complications.</div></front></TEI><double doi="10.1002/mds.870130307"><ISTEX><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">A trial of dextromethorphan in parkinsonian patients with motor response complications</title><author><name sortKey="Metman, Leo Verhagen" sort="Metman, Leo Verhagen" uniqKey="Metman L" first="Leo Verhagen" last="Metman">Leo Verhagen Metman</name></author><author><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name></author><author><name sortKey="Van Den Munckhof, Pep N" sort="Van Den Munckhof, Pep N" uniqKey="Van Den Munckhof P" first="Pep N" last="Van Den Munckhof">Pep N Van Den Munckhof</name></author><author><name sortKey="Dotto, Paolo Del" sort="Dotto, Paolo Del" uniqKey="Dotto P" first="Paolo Del" last="Dotto">Paolo Del Dotto</name></author><author><name sortKey="Natte, Remco" sort="Natte, Remco" uniqKey="Natte R" first="Remco" last="Natté">Remco Natté</name></author><author><name sortKey="Chase, Thomas N" sort="Chase, Thomas N" uniqKey="Chase T" first="Thomas N." last="Chase">Thomas N. Chase</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:6678D223545AE509A9A53066038F609551C223B3</idno><date when="1998" year="1998">1998</date><idno type="doi">10.1002/mds.870130307</idno><idno type="url">https://api.istex.fr/document/6678D223545AE509A9A53066038F609551C223B3/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002A80</idno><idno type="wicri:Area/Istex/Curation">002A80</idno><idno type="wicri:Area/Istex/Checkpoint">003828</idno><idno type="wicri:doubleKey">0885-3185:1998:Metman L:a:trial:of</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">A trial of dextromethorphan in parkinsonian patients with motor response complications</title><author><name sortKey="Metman, Leo Verhagen" sort="Metman, Leo Verhagen" uniqKey="Metman L" first="Leo Verhagen" last="Metman">Leo Verhagen Metman</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Blanchet, Pierre J" sort="Blanchet, Pierre J" uniqKey="Blanchet P" first="Pierre J." last="Blanchet">Pierre J. Blanchet</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Van Den Munckhof, Pep N" sort="Van Den Munckhof, Pep N" uniqKey="Van Den Munckhof P" first="Pep N" last="Van Den Munckhof">Pep N Van Den Munckhof</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Dotto, Paolo Del" sort="Dotto, Paolo Del" uniqKey="Dotto P" first="Paolo Del" last="Dotto">Paolo Del Dotto</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Natte, Remco" sort="Natte, Remco" uniqKey="Natte R" first="Remco" last="Natté">Remco Natté</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Chase, Thomas N" sort="Chase, Thomas N" uniqKey="Chase T" first="Thomas N." last="Chase">Thomas N. Chase</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="1998-05">1998-05</date><biblScope unit="vol">13</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="414">414</biblScope><biblScope unit="page" to="417">417</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">6678D223545AE509A9A53066038F609551C223B3</idno><idno type="DOI">10.1002/mds.870130307</idno><idno type="ArticleID">MDS870130307</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Glutamate</term><term>Motor complications</term><term>NMDA</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The effects of the NMDA antagonist dextromethorphan (DM) on levodopa‐associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open‐label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60–120 mg/day). The 12 remaining patients either experinced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double‐blind, placebo‐controlled, crossover study with two 2‐week arms separted by 1 week wash‐out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% accfording to UPDRS interviews, without compromising the anti‐Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa‐associated motor complications.</div></front></TEI></ISTEX><PubMed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A trial of dextromethorphan in parkinsonian patients with motor response complications.</title><author><name sortKey="Verhagen Metman, L" sort="Verhagen Metman, L" uniqKey="Verhagen Metman L" first="L" last="Verhagen Metman">L. Verhagen Metman</name><affiliation wicri:level="1"><nlm:affiliation>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406</wicri:regionArea><wicri:noRegion>Maryland 20892-1406</wicri:noRegion></affiliation></author><author><name sortKey="Blanchet, P J" sort="Blanchet, P J" uniqKey="Blanchet P" first="P J" last="Blanchet">P J Blanchet</name></author><author><name sortKey="Van Den Munckhof, P" sort="Van Den Munckhof, P" uniqKey="Van Den Munckhof P" first="P" last="Van Den Munckhof">P. Van Den Munckhof</name></author><author><name sortKey="Del Dotto, P" sort="Del Dotto, P" uniqKey="Del Dotto P" first="P" last="Del Dotto">P. Del Dotto</name></author><author><name sortKey="Natte, R" sort="Natte, R" uniqKey="Natte R" first="R" last="Natté">R. Natté</name></author><author><name sortKey="Chase, T N" sort="Chase, T N" uniqKey="Chase T" first="T N" last="Chase">T N Chase</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1998">1998</date><idno type="RBID">pubmed:9613730</idno><idno type="pmid">9613730</idno><idno type="doi">10.1002/mds.870130307</idno><idno type="wicri:Area/PubMed/Corpus">004431</idno><idno type="wicri:Area/PubMed/Curation">004431</idno><idno type="wicri:Area/PubMed/Checkpoint">004515</idno><idno type="wicri:Area/Ncbi/Merge">004F52</idno><idno type="wicri:Area/Ncbi/Curation">004F52</idno><idno type="wicri:Area/Ncbi/Checkpoint">004F52</idno><idno type="wicri:doubleKey">0885-3185:1998:Verhagen Metman L:a:trial:of</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A trial of dextromethorphan in parkinsonian patients with motor response complications.</title><author><name sortKey="Verhagen Metman, L" sort="Verhagen Metman, L" uniqKey="Verhagen Metman L" first="L" last="Verhagen Metman">L. Verhagen Metman</name><affiliation wicri:level="1"><nlm:affiliation>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406</wicri:regionArea><wicri:noRegion>Maryland 20892-1406</wicri:noRegion></affiliation></author><author><name sortKey="Blanchet, P J" sort="Blanchet, P J" uniqKey="Blanchet P" first="P J" last="Blanchet">P J Blanchet</name></author><author><name sortKey="Van Den Munckhof, P" sort="Van Den Munckhof, P" uniqKey="Van Den Munckhof P" first="P" last="Van Den Munckhof">P. Van Den Munckhof</name></author><author><name sortKey="Del Dotto, P" sort="Del Dotto, P" uniqKey="Del Dotto P" first="P" last="Del Dotto">P. Del Dotto</name></author><author><name sortKey="Natte, R" sort="Natte, R" uniqKey="Natte R" first="R" last="Natté">R. Natté</name></author><author><name sortKey="Chase, T N" sort="Chase, T N" uniqKey="Chase T" first="T N" last="Chase">T N Chase</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="1998" type="published">1998</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Activities of Daily Living (classification)</term><term>Aged</term><term>Antiparkinson Agents (adverse effects)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Carbidopa (adverse effects)</term><term>Carbidopa (therapeutic use)</term><term>Cross-Over Studies</term><term>Dextromethorphan (adverse effects)</term><term>Dextromethorphan (therapeutic use)</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Therapy, Combination</term><term>Dyskinesia, Drug-Induced (diagnosis)</term><term>Dyskinesia, Drug-Induced (drug therapy)</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Motor Skills (drug effects)</term><term>N-Methylaspartate (antagonists & inhibitors)</term><term>Neurologic Examination (drug effects)</term><term>Parkinson Disease (diagnosis)</term><term>Parkinson Disease (drug therapy)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Dextromethorphan</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>N-Methylaspartate</term></keywords><keywords scheme="MESH" qualifier="classification" xml:lang="en"><term>Activities of Daily Living</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Motor Skills</term><term>Neurologic Examination</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Carbidopa</term><term>Dextromethorphan</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Cross-Over Studies</term><term>Dose-Response Relationship, Drug</term><term>Double-Blind Method</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications.</div></front></TEI></PubMed></double></record>Pour manipuler ce document sous Unix (Dilib)
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