The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of L-dopa in the MPTP-lesioned primate model of Parkinson's disease.
Identifieur interne : 004B93 ( Main/Exploration ); précédent : 004B92; suivant : 004B94The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of L-dopa in the MPTP-lesioned primate model of Parkinson's disease.
Auteurs : B. Henry [Royaume-Uni] ; S H Fox ; D. Peggs ; A R Crossman ; J M BrotchieSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1999.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacokinetics), Adrenergic Antagonists (pharmacology), Adrenergic Antagonists (therapeutic use), Animals, Antiparkinson Agents (metabolism), Brain (metabolism), Callithrix, Disease Models, Animal, Disease Progression, Dose-Response Relationship, Drug, Drug Synergism, Dyskinesias (drug therapy), Female, Idazoxan (pharmacology), Idazoxan (therapeutic use), Levodopa (metabolism), Male, Receptors, Adrenergic, alpha-2 (drug effects), Time Factors, Yohimbine (pharmacology), Yohimbine (therapeutic use).
- MESH :
- chemical , drug effects : Receptors, Adrenergic, alpha-2.
- chemical , metabolism : Antiparkinson Agents, Levodopa.
- chemical , pharmacokinetics : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- chemical , pharmacology : Adrenergic Antagonists, Idazoxan, Yohimbine.
- chemical , therapeutic use : Adrenergic Antagonists, Idazoxan, Yohimbine.
- drug therapy : Dyskinesias.
- metabolism : Brain.
- Animals, Callithrix, Disease Models, Animal, Disease Progression, Dose-Response Relationship, Drug, Drug Synergism, Female, Male, Time Factors.
Abstract
Dopamine replacement therapy in patients with Parkinson's disease is plagued by the emergence of abnormal involuntary movements known as L-dopa-induced dyskinesias. It has been demonstrated that yohimbine can reduce L-dopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. Yohimbine is, among other things, an alpha-adrenergic receptor antagonist. In this study, we demonstrate that the selective and potent alpha2-adrenergic receptor antagonist idazoxan reduces L-dopa-induced dyskinesia in the MPTP-lesioned marmoset model of Parkinson's disease. The alpha2-adrenergic receptor antagonists rauwolscine and yohimbine also reduce L-dopa-induced dyskinesia. Furthermore, we demonstrate that coadministration of idazoxan with L-dopa can provide an anti-parkinsonian action more than twice the length of that seen with L-dopa alone. However, idazoxan as a monotherapy displayed no anti-parkinsonian actions. We propose that idazoxan in combination with L-dopa may provide a novel approach to the treatment of Parkinson's disease that will not only reduce the dyskinetic side effects, but extend the anti-parkinsonian actions of L-dopa. Idazoxan, as an adjunct to dopamine replacement, may prove useful in the treatment of parkinsonian patients at all stages of disease progression.
PubMed: 10495035
Affiliations:
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Peggs</name></author><author><name sortKey="Crossman, A R" sort="Crossman, A R" uniqKey="Crossman A" first="A R" last="Crossman">A R Crossman</name></author><author><name sortKey="Brotchie, J M" sort="Brotchie, J M" uniqKey="Brotchie J" first="J M" last="Brotchie">J M Brotchie</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1999">1999</date><idno type="RBID">pubmed:10495035</idno><idno type="pmid">10495035</idno><idno type="wicri:Area/PubMed/Corpus">004134</idno><idno type="wicri:Area/PubMed/Curation">004134</idno><idno type="wicri:Area/PubMed/Checkpoint">004092</idno><idno type="wicri:Area/Ncbi/Merge">000117</idno><idno type="wicri:Area/Ncbi/Curation">000117</idno><idno type="wicri:Area/Ncbi/Checkpoint">000117</idno><idno type="wicri:doubleKey">0885-3185:1999:Henry B:the:alpha:adrenergic</idno><idno type="wicri:Area/Main/Merge">007699</idno><idno type="wicri:Area/Main/Curation">004B93</idno><idno type="wicri:Area/Main/Exploration">004B93</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of L-dopa in the MPTP-lesioned primate model of Parkinson's disease.</title><author><name sortKey="Henry, B" sort="Henry, B" uniqKey="Henry B" first="B" last="Henry">B. Henry</name><affiliation wicri:level="1"><nlm:affiliation>Organon Laboratories Limited, Department of Pharmacology, Lanarkshire, Scotland, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Organon Laboratories Limited, Department of Pharmacology, Lanarkshire, Scotland</wicri:regionArea><wicri:noRegion>Scotland</wicri:noRegion></affiliation></author><author><name sortKey="Fox, S H" sort="Fox, S H" uniqKey="Fox S" first="S H" last="Fox">S H Fox</name></author><author><name sortKey="Peggs, D" sort="Peggs, D" uniqKey="Peggs D" first="D" last="Peggs">D. Peggs</name></author><author><name sortKey="Crossman, A R" sort="Crossman, A R" uniqKey="Crossman A" first="A R" last="Crossman">A R Crossman</name></author><author><name sortKey="Brotchie, J M" sort="Brotchie, J M" uniqKey="Brotchie J" first="J M" last="Brotchie">J M Brotchie</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="1999" type="published">1999</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacokinetics)</term><term>Adrenergic Antagonists (pharmacology)</term><term>Adrenergic Antagonists (therapeutic use)</term><term>Animals</term><term>Antiparkinson Agents (metabolism)</term><term>Brain (metabolism)</term><term>Callithrix</term><term>Disease Models, Animal</term><term>Disease Progression</term><term>Dose-Response Relationship, Drug</term><term>Drug Synergism</term><term>Dyskinesias (drug therapy)</term><term>Female</term><term>Idazoxan (pharmacology)</term><term>Idazoxan (therapeutic use)</term><term>Levodopa (metabolism)</term><term>Male</term><term>Receptors, Adrenergic, alpha-2 (drug effects)</term><term>Time Factors</term><term>Yohimbine (pharmacology)</term><term>Yohimbine (therapeutic use)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Adrenergic, alpha-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adrenergic Antagonists</term><term>Idazoxan</term><term>Yohimbine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Adrenergic Antagonists</term><term>Idazoxan</term><term>Yohimbine</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Dyskinesias</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Callithrix</term><term>Disease Models, Animal</term><term>Disease Progression</term><term>Dose-Response Relationship, Drug</term><term>Drug Synergism</term><term>Female</term><term>Male</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Dopamine replacement therapy in patients with Parkinson's disease is plagued by the emergence of abnormal involuntary movements known as L-dopa-induced dyskinesias. It has been demonstrated that yohimbine can reduce L-dopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. Yohimbine is, among other things, an alpha-adrenergic receptor antagonist. In this study, we demonstrate that the selective and potent alpha2-adrenergic receptor antagonist idazoxan reduces L-dopa-induced dyskinesia in the MPTP-lesioned marmoset model of Parkinson's disease. The alpha2-adrenergic receptor antagonists rauwolscine and yohimbine also reduce L-dopa-induced dyskinesia. Furthermore, we demonstrate that coadministration of idazoxan with L-dopa can provide an anti-parkinsonian action more than twice the length of that seen with L-dopa alone. However, idazoxan as a monotherapy displayed no anti-parkinsonian actions. We propose that idazoxan in combination with L-dopa may provide a novel approach to the treatment of Parkinson's disease that will not only reduce the dyskinetic side effects, but extend the anti-parkinsonian actions of L-dopa. Idazoxan, as an adjunct to dopamine replacement, may prove useful in the treatment of parkinsonian patients at all stages of disease progression.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><noCountry><name sortKey="Brotchie, J M" sort="Brotchie, J M" uniqKey="Brotchie J" first="J M" last="Brotchie">J M Brotchie</name><name sortKey="Crossman, A R" sort="Crossman, A R" uniqKey="Crossman A" first="A R" last="Crossman">A R Crossman</name><name sortKey="Fox, S H" sort="Fox, S H" uniqKey="Fox S" first="S H" last="Fox">S H Fox</name><name sortKey="Peggs, D" sort="Peggs, D" uniqKey="Peggs D" first="D" last="Peggs">D. Peggs</name></noCountry><country name="Royaume-Uni"><noRegion><name sortKey="Henry, B" sort="Henry, B" uniqKey="Henry B" first="B" last="Henry">B. Henry</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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