The α2 Adrenergic Antagonist Fipamezole Improves Quality of Levodopa Action in Parkinsonian Primates
Identifieur interne : 002368 ( Main/Merge ); précédent : 002367; suivant : 002369The α2 Adrenergic Antagonist Fipamezole Improves Quality of Levodopa Action in Parkinsonian Primates
Auteurs : Tom H. Johnston [Canada] ; Susan H. Fox [Canada] ; Matthew J. Piggott [Australie] ; Juha-Matti Savola [Suisse] ; Jonathan M. Brotchie [Canada]Source :
- Movement disorders [ 0885-3185 ] ; 2010.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Reduction in the antiparkinsonian benefit of levodopa is a major complication of long-term levodopa treatment in advanced Parkinson's disease (PD). Such loss of benefit arises because of reduced duration of action and appearance of disabling dyskinesia. We assess the potential of the α2 adrenergic antagonist fipamezole to reduce motor complications in parkinsonian macaques. MPTP-lesioned macaques were treated acutely with fipamezole (10 mg/kg) alone and in combination with two doses of levodopa. Fipamezole extended both duration and quality of antiparkinsonian action of levodopa. Duration of antiparkinsonian action, on time, was increased by up to 75% while "good-quality" on time, i.e., that not associated with disabling dyskinesia, was increased by up to 98%. Combination of fipamezole with the lower dose of levodopa provided antiparkinsonian benefit at least equivalent to that provided by the higher dose levodopa alone. However, with the combination, antiparkinsonian benefit was of much better quality. The proportion of on time without disabling dyskinesia (79%) was significantly greater than that with high dose levodopa alone (45%). Increased duration and quality of levodopa action may represent therapeutically valuable actions of α2 adrenergic antagonists.
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Pascal:10-0474325Le document en format XML
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Adrenergic Antagonist Fipamezole Improves Quality of Levodopa Action in Parkinsonian Primates</title>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">The α<sub>2</sub>
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<series><title level="j" type="main">Movement disorders</title>
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<term>Parkinson disease</term>
<term>Primates</term>
<term>α2-Adrenergic receptor</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term>
<term>Dyskinésie</term>
<term>Pathologie du système nerveux</term>
<term>Récepteur α2-adrénergique</term>
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<front><div type="abstract" xml:lang="en">Reduction in the antiparkinsonian benefit of levodopa is a major complication of long-term levodopa treatment in advanced Parkinson's disease (PD). Such loss of benefit arises because of reduced duration of action and appearance of disabling dyskinesia. We assess the potential of the α<sub>2</sub>
adrenergic antagonist fipamezole to reduce motor complications in parkinsonian macaques. MPTP-lesioned macaques were treated acutely with fipamezole (10 mg/kg) alone and in combination with two doses of levodopa. Fipamezole extended both duration and quality of antiparkinsonian action of levodopa. Duration of antiparkinsonian action, on time, was increased by up to 75% while "good-quality" on time, i.e., that not associated with disabling dyskinesia, was increased by up to 98%. Combination of fipamezole with the lower dose of levodopa provided antiparkinsonian benefit at least equivalent to that provided by the higher dose levodopa alone. However, with the combination, antiparkinsonian benefit was of much better quality. The proportion of on time without disabling dyskinesia (79%) was significantly greater than that with high dose levodopa alone (45%). Increased duration and quality of levodopa action may represent therapeutically valuable actions of α<sub>2</sub>
adrenergic antagonists.</div>
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