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.
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1406, USA.
P J
PJ
Blanchet
S
S
Konitsiotis
T N
TN
Chase
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