Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys

• Published in: Movement disorders Vol. 13; no. 5; p. 798
• Main Authors: Blanchet, P J, Konitsiotis, S, Chase, T N
• Format: Journal Article
• Language: English
• Published: United States 01.09.1998
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Amantadine - administration & dosage; Amantadine - adverse effects; Animals; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - adverse effects; Dopamine Agents - administration & dosage; Dopamine Agents - adverse effects; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced - drug therapy; Dyskinesia, Drug-Induced - physiopathology; Injections, Subcutaneous; Levodopa - administration & dosage; Levodopa - adverse effects; Macaca fascicularis; Neurologic Examination - drug effects; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - drug therapy; Parkinson Disease, Secondary - physiopathology; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - physiology
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.870130507

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.