Abstract
The antidyskinetic potential of the glutamate NMDA receptor channel blocker amantadine was evaluated in four levodopa-primed parkinsonian monkeys using two different regimens (1.25 or 2.5 mg/kg administered subcutaneously twice daily for 3-6 days). When administered with a relatively low dose of levodopa, amantadine produced a near-total suppression of choreiform dyskinesias and a substantial reduction in dystonic dyskinesias at the expense of a significant reduction in antiparkinsonian response. With a high dose of levodopa, amantadine had a smaller but still significant effect on dyskinesias without altering the antiparkinsonian response. These results lend support to the view that glutamate receptor-mediated mechanisms contribute to levodopa-induced dyskinesias. They also suggest that amantadine could alleviate such complications in parkinsonian patients, especially with careful dose optimization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Amantadine / administration & dosage*
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Amantadine / adverse effects
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Animals
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Antiparkinson Agents / administration & dosage
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Antiparkinson Agents / adverse effects*
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Dopamine Agents / administration & dosage*
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Dopamine Agents / adverse effects
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Dose-Response Relationship, Drug
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Dyskinesia, Drug-Induced / drug therapy*
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Dyskinesia, Drug-Induced / physiopathology
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Injections, Subcutaneous
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Levodopa / administration & dosage
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Levodopa / adverse effects*
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Macaca fascicularis
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Neurologic Examination / drug effects
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Parkinson Disease, Secondary / chemically induced
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Parkinson Disease, Secondary / drug therapy*
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Parkinson Disease, Secondary / physiopathology
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / physiology
Substances
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Antiparkinson Agents
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Dopamine Agents
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Receptors, N-Methyl-D-Aspartate
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Levodopa
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Amantadine