Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys.
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.
Blanchet
P J
PJ
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1406, USA.
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000547:Amantadine / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000503:physiopathology; D007279:Injections, Subcutaneous; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects*; D008252:Macaca fascicularis; D009460:Neurologic Examination / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000547:Amantadine