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 : 007699 ( Main/Merge ); précédent : 007698; suivant : 007700The 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
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pubmed:10495035Le document en format XML
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<author><name sortKey="Fox, S H" sort="Fox, S H" uniqKey="Fox S" first="S H" last="Fox">S H Fox</name>
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<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>
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