Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease
Identifieur interne : 006E79 ( Main/Merge ); précédent : 006E78; suivant : 006E80Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease
Auteurs : Olivier Rascol [France] ; I. Arnulf [France] ; H. Peyro-Saint Paul [France] ; C. Brefel-Courbon [France] ; M. Vidailhet [France] ; C. Thalamas [France] ; A. M. Bonnet [France] ; S. Descombes [France] ; B. Bejjani [France] ; N. Fabre [France] ; J. L. Montastruc [France] ; Yves Agid [France]Source :
- Movement disorders [ 0885-3185 ] ; 2001.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
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Abstract
Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopa-therapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dys-kinetic patients with Parkinson's disease.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease</title><author><name sortKey="Rascol, O" sort="Rascol, O" uniqKey="Rascol O" first="O." last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Midi-Pyrénées</region></placeName><orgName type="university" n="3">Université Toulouse III - Paul Sabatier</orgName><orgName type="institution" wicri:auto="newGroup">Université de Toulouse</orgName></affiliation></author><author><name sortKey="Arnulf, I" sort="Arnulf, I" uniqKey="Arnulf I" first="I." last="Arnulf">I. 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Bonnet</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Clinical Investigation Centre and INSERM U289, University Hospital of Pitie-Salpetriere</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Descombes, S" sort="Descombes, S" uniqKey="Descombes S" first="S." last="Descombes">S. Descombes</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Bejjani, B" sort="Bejjani, B" uniqKey="Bejjani B" first="B." last="Bejjani">B. Bejjani</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Clinical Investigation Centre and INSERM U289, University Hospital of Pitie-Salpetriere</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Fabre, N" sort="Fabre, N" uniqKey="Fabre N" first="N." last="Fabre">N. 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Montastruc</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Yves Agid</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Clinical Investigation Centre and INSERM U289, University Hospital of Pitie-Salpetriere</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Paris</settlement></placeName><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">01-0429759</idno><date when="2001">2001</date><idno type="stanalyst">PASCAL 01-0429759 INIST</idno><idno type="RBID">Pascal:01-0429759</idno><idno type="wicri:Area/PascalFrancis/Corpus">002966</idno><idno type="wicri:Area/PascalFrancis/Curation">000355</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">002980</idno><idno type="wicri:doubleKey">0885-3185:2001:Rascol O:idazoxan:an:alpha</idno><idno type="wicri:Area/Main/Merge">006E79</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson's disease</title><author><name sortKey="Rascol, O" sort="Rascol, O" uniqKey="Rascol O" first="O." last="Rascol">Olivier Rascol</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Midi-Pyrénées</region></placeName><orgName type="university" n="3">Université Toulouse III - Paul Sabatier</orgName><orgName type="institution" wicri:auto="newGroup">Université de Toulouse</orgName></affiliation></author><author><name sortKey="Arnulf, I" sort="Arnulf, I" uniqKey="Arnulf I" first="I." last="Arnulf">I. Arnulf</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Clinical Investigation Centre and INSERM U289, University Hospital of Pitie-Salpetriere</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Paul, H Peyro Saint" sort="Paul, H Peyro Saint" uniqKey="Paul H" first="H. Peyro-Saint" last="Paul">H. Peyro-Saint Paul</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Institut de recherche Pierre Fabre</s1><s2>Boulogne</s2><s3>FRA</s3><sZ>3 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>Boulogne</wicri:noRegion><wicri:noRegion>Institut de recherche Pierre Fabre</wicri:noRegion><wicri:noRegion>Institut de recherche Pierre Fabre</wicri:noRegion></affiliation></author><author><name sortKey="Brefel Courbon, C" sort="Brefel Courbon, C" uniqKey="Brefel Courbon C" first="C." last="Brefel-Courbon">C. Brefel-Courbon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Vidailhet, M" sort="Vidailhet, M" uniqKey="Vidailhet M" first="M." last="Vidailhet">M. Vidailhet</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Clinical Investigation Centre and INSERM U289, University Hospital of Pitie-Salpetriere</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Thalamas, C" sort="Thalamas, C" uniqKey="Thalamas C" first="C." last="Thalamas">C. Thalamas</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Bonnet, A M" sort="Bonnet, A M" uniqKey="Bonnet A" first="A. M." last="Bonnet">A. M. Bonnet</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Clinical Investigation Centre and INSERM U289, University Hospital of Pitie-Salpetriere</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Descombes, S" sort="Descombes, S" uniqKey="Descombes S" first="S." last="Descombes">S. Descombes</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Bejjani, B" sort="Bejjani, B" uniqKey="Bejjani B" first="B." last="Bejjani">B. Bejjani</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Clinical Investigation Centre and INSERM U289, University Hospital of Pitie-Salpetriere</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Fabre, N" sort="Fabre, N" uniqKey="Fabre N" first="N." last="Fabre">N. Fabre</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Montastruc, J L" sort="Montastruc, J L" uniqKey="Montastruc J" first="J. L." last="Montastruc">J. L. Montastruc</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Clinical Pharmacology, Clinical Investigation Centre and INSERM U455, University Hospital</s1><s2>Toulouse</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Yves Agid</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Neurology, Clinical Investigation Centre and INSERM U289, University Hospital of Pitie-Salpetriere</s1><s2>Paris</s2><s3>FRA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><settlement type="city">Paris</settlement></placeName><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2001">2001</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antagonist</term><term>Chemotherapy</term><term>Dyskinesia</term><term>Human</term><term>Idazoxan</term><term>Parkinson disease</term><term>Phase II trial</term><term>Treatment</term><term>α2-Adrenergic receptor</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Parkinson maladie</term><term>Dyskinésie</term><term>Idazoxan</term><term>Antagoniste</term><term>Récepteur α2-adrénergique</term><term>Chimiothérapie</term><term>Traitement</term><term>Homme</term><term>Essai clinique phase II</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopa-therapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dys-kinetic patients with Parkinson's disease.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Midi-Pyrénées</li><li>Île-de-France</li></region><settlement><li>Paris</li><li>Toulouse</li></settlement><orgName><li>Hôpital de la Salpêtrière</li><li>Université Toulouse III - Paul Sabatier</li><li>Université de Toulouse</li></orgName></list><tree><country name="France"><noRegion><name sortKey="Rascol, O" sort="Rascol, O" uniqKey="Rascol O" first="O." last="Rascol">Olivier Rascol</name></noRegion><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Yves Agid</name><name sortKey="Arnulf, I" sort="Arnulf, I" uniqKey="Arnulf I" first="I." last="Arnulf">I. Arnulf</name><name sortKey="Bejjani, B" sort="Bejjani, B" uniqKey="Bejjani B" first="B." last="Bejjani">B. Bejjani</name><name sortKey="Bonnet, A M" sort="Bonnet, A M" uniqKey="Bonnet A" first="A. M." last="Bonnet">A. M. Bonnet</name><name sortKey="Brefel Courbon, C" sort="Brefel Courbon, C" uniqKey="Brefel Courbon C" first="C." last="Brefel-Courbon">C. Brefel-Courbon</name><name sortKey="Descombes, S" sort="Descombes, S" uniqKey="Descombes S" first="S." last="Descombes">S. Descombes</name><name sortKey="Fabre, N" sort="Fabre, N" uniqKey="Fabre N" first="N." last="Fabre">N. Fabre</name><name sortKey="Montastruc, J L" sort="Montastruc, J L" uniqKey="Montastruc J" first="J. L." last="Montastruc">J. L. Montastruc</name><name sortKey="Paul, H Peyro Saint" sort="Paul, H Peyro Saint" uniqKey="Paul H" first="H. Peyro-Saint" last="Paul">H. Peyro-Saint Paul</name><name sortKey="Thalamas, C" sort="Thalamas, C" uniqKey="Thalamas C" first="C." last="Thalamas">C. Thalamas</name><name sortKey="Vidailhet, M" sort="Vidailhet, M" uniqKey="Vidailhet M" first="M." last="Vidailhet">M. 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