The L‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and dopamine receptor resensitization
Identifieur interne : 002833 ( Istex/Checkpoint ); précédent : 002832; suivant : 002834The L‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and dopamine receptor resensitization
Auteurs : L. Direnfeld [Canada] ; L. Spero [Canada] ; J. Marotta [Canada] ; J. Seeman [Canada]Source :
- [ 0364-5134 ]
Abstract
It has been suggested that patients with Parkinson disease partially compensate for neuron loss by developing denervation supersensitivity, and, if so, that prolonged levodopa (L‐dopa) therapy might lead to desensitization. As a preliminary test of this hypothesis, and in order to study whether it was possible to “resensitize” a patient who had already presumbly been desensitized by previous L‐dopa therapy, a patient who had become unpredictably responsive to L‐dopa was investigated. The patient had been taking L‐dopa for eight years and had exhibited severe dyskinesia‐akinesia oscillation (“on‐off” phenomenon) before the study. There was no consistent response to his hourly doses of Prolopa (L‐dopa and benserazide in a 4:1 ratio). He was first lowered, over 33 days, to 20% of his original Prolopa dose. The dosage was then increased until a consistent response were observed. The three main results achieved were, first, overall reduction by 64% of the daily requirement for L‐dopa; second, conversion from a previously unpredictable to a predictable response to each dose of L‐dopa; and, third, change in his movement fluctuations to a pattern more typical of “end‐of‐dose” akinesia than the “on‐off” phenomenon. The results support the idea of dopamine receptor resensitization upon reduction of the L‐dopa dosage.
Url:
DOI: 10.1002/ana.410040619
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
ISTEX:EB08FE3C3B4F4238A0B389305C093117F8EC3C5ALe document en format XML
<record><TEI wicri:istexFullTextTei="no"><teiHeader><fileDesc><titleStmt><title xml:lang="en">The L‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and dopamine receptor resensitization</title><author><name sortKey="Direnfeld, L" sort="Direnfeld, L" uniqKey="Direnfeld L" first="L." last="Direnfeld">L. Direnfeld</name></author><author><name sortKey="Spero, L" sort="Spero, L" uniqKey="Spero L" first="L." last="Spero">L. Spero</name></author><author><name sortKey="Marotta, J" sort="Marotta, J" uniqKey="Marotta J" first="J." last="Marotta">J. Marotta</name></author><author><name sortKey="Seeman, J" sort="Seeman, J" uniqKey="Seeman J" first="J." last="Seeman">J. Seeman</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:EB08FE3C3B4F4238A0B389305C093117F8EC3C5A</idno><date when="1978" year="1978">1978</date><idno type="doi">10.1002/ana.410040619</idno><idno type="url">https://api-v5.istex.fr/document/EB08FE3C3B4F4238A0B389305C093117F8EC3C5A/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000313</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000313</idno><idno type="wicri:Area/Istex/Curation">000313</idno><idno type="wicri:Area/Istex/Checkpoint">002833</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">002833</idno></publicationStmt><sourceDesc><biblStruct><analytic><author><name sortKey="Direnfeld, L" sort="Direnfeld, L" uniqKey="Direnfeld L" first="L." last="Direnfeld">L. Direnfeld</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology, St. Michael's Hospital, and the Department of Pharmacology, University of Toronto Faculty of Medicine, Toronto, Ont</wicri:regionArea><wicri:noRegion>Ont</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Spero, L" sort="Spero, L" uniqKey="Spero L" first="L." last="Spero">L. Spero</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology, St. Michael's Hospital, and the Department of Pharmacology, University of Toronto Faculty of Medicine, Toronto, Ont</wicri:regionArea><wicri:noRegion>Ont</wicri:noRegion></affiliation></author><author><name sortKey="Marotta, J" sort="Marotta, J" uniqKey="Marotta J" first="J." last="Marotta">J. Marotta</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology, St. Michael's Hospital, and the Department of Pharmacology, University of Toronto Faculty of Medicine, Toronto, Ont</wicri:regionArea><wicri:noRegion>Ont</wicri:noRegion></affiliation></author><author><name sortKey="Seeman, J" sort="Seeman, J" uniqKey="Seeman J" first="J." last="Seeman">J. Seeman</name><affiliation wicri:level="1"><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology, St. Michael's Hospital, and the Department of Pharmacology, University of Toronto Faculty of Medicine, Toronto, Ont</wicri:regionArea><wicri:noRegion>Ont</wicri:noRegion></affiliation><affiliation wicri:level="1"><country>Canada</country><wicri:regionArea>Department of Pharmacology, University of Toronto Faculty of Medicine, Toronto, Ont</wicri:regionArea><wicri:noRegion>Ont</wicri:noRegion></affiliation></author></analytic><series><idno type="ISSN">0364-5134</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">It has been suggested that patients with Parkinson disease partially compensate for neuron loss by developing denervation supersensitivity, and, if so, that prolonged levodopa (L‐dopa) therapy might lead to desensitization. As a preliminary test of this hypothesis, and in order to study whether it was possible to “resensitize” a patient who had already presumbly been desensitized by previous L‐dopa therapy, a patient who had become unpredictably responsive to L‐dopa was investigated. The patient had been taking L‐dopa for eight years and had exhibited severe dyskinesia‐akinesia oscillation (“on‐off” phenomenon) before the study. There was no consistent response to his hourly doses of Prolopa (L‐dopa and benserazide in a 4:1 ratio). He was first lowered, over 33 days, to 20% of his original Prolopa dose. The dosage was then increased until a consistent response were observed. The three main results achieved were, first, overall reduction by 64% of the daily requirement for L‐dopa; second, conversion from a previously unpredictable to a predictable response to each dose of L‐dopa; and, third, change in his movement fluctuations to a pattern more typical of “end‐of‐dose” akinesia than the “on‐off” phenomenon. The results support the idea of dopamine receptor resensitization upon reduction of the L‐dopa dosage.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Direnfeld, L" sort="Direnfeld, L" uniqKey="Direnfeld L" first="L." last="Direnfeld">L. Direnfeld</name></noRegion><name sortKey="Marotta, J" sort="Marotta, J" uniqKey="Marotta J" first="J." last="Marotta">J. Marotta</name><name sortKey="Seeman, J" sort="Seeman, J" uniqKey="Seeman J" first="J." last="Seeman">J. Seeman</name><name sortKey="Seeman, J" sort="Seeman, J" uniqKey="Seeman J" first="J." last="Seeman">J. Seeman</name><name sortKey="Spero, L" sort="Spero, L" uniqKey="Spero L" first="L." last="Spero">L. Spero</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Istex/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002833 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Checkpoint/biblio.hfd -nk 002833 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Istex
|étape= Checkpoint
|type= RBID
|clé= ISTEX:EB08FE3C3B4F4238A0B389305C093117F8EC3C5A
|texte= The L‐dopa on‐off effect in parkinson disease: Treatment by transient drug withdrawal and dopamine receptor resensitization
}}
| This area was generated with Dilib version V0.6.29. |  |