Tags

Type your tag names separated by a space and hit enter

Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys.
Ann Neurol. 1996 May; 39(5):574-8.AN

Abstract

Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor have been reported to potentiate the antiparkinsonian action of levodopa and reverse levodopa-induced motor fluctuations in animal models of Parkinson's disease. To evaluate the effect of NMDA receptor blockade on dyskinesias complicating the response to long-term levodopa therapy, we studied the selective antagonist LY235959 in six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. Drugs were administered subcutaneously, LY235959 at doses of 0.5, 1.0, 3.0, and 5.0 mg/kg and levodopa/benserazide at doses that produced moderate dyskinesias while almost totally reversing parkinsonian signs. Compared with vehicle control injections, LY235959 (3.0 mg/kg) abolished oral dyskinesias and diminished choreic dyskinesias by 68% (p < 0.01). Lower doses had smaller effects, although still significant, on oral dyskinesias (55% reduction at 1.0 mg/kg, p < 0.05). The highest LY235959 dose (5.0 mg/kg) prolonged oral dyskinesia suppression, but tended to increase dystonia severity. LY235959 had no effect on motor function when given alone and did not reduce the antiparkinsonian response to levodopa. These findings suggest that NMDA receptor blockade may ameliorate the dyskinetic complications of long-term levodopa therapy, without diminishing the beneficial effects on parkinsonian signs.

Authors+Show Affiliations

Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8619541

Citation

Papa, S M., and T N. Chase. "Levodopa-induced Dyskinesias Improved By a Glutamate Antagonist in Parkinsonian Monkeys." Annals of Neurology, vol. 39, no. 5, 1996, pp. 574-8.
Papa SM, Chase TN. Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. Ann Neurol. 1996;39(5):574-8.
Papa, S. M., & Chase, T. N. (1996). Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. Annals of Neurology, 39(5), 574-8.
Papa SM, Chase TN. Levodopa-induced Dyskinesias Improved By a Glutamate Antagonist in Parkinsonian Monkeys. Ann Neurol. 1996;39(5):574-8. PubMed PMID: 8619541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. AU - Papa,S M, AU - Chase,T N, PY - 1996/5/1/pubmed PY - 1996/5/1/medline PY - 1996/5/1/entrez SP - 574 EP - 8 JF - Annals of neurology JO - Ann Neurol VL - 39 IS - 5 N2 - Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor have been reported to potentiate the antiparkinsonian action of levodopa and reverse levodopa-induced motor fluctuations in animal models of Parkinson's disease. To evaluate the effect of NMDA receptor blockade on dyskinesias complicating the response to long-term levodopa therapy, we studied the selective antagonist LY235959 in six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. Drugs were administered subcutaneously, LY235959 at doses of 0.5, 1.0, 3.0, and 5.0 mg/kg and levodopa/benserazide at doses that produced moderate dyskinesias while almost totally reversing parkinsonian signs. Compared with vehicle control injections, LY235959 (3.0 mg/kg) abolished oral dyskinesias and diminished choreic dyskinesias by 68% (p < 0.01). Lower doses had smaller effects, although still significant, on oral dyskinesias (55% reduction at 1.0 mg/kg, p < 0.05). The highest LY235959 dose (5.0 mg/kg) prolonged oral dyskinesia suppression, but tended to increase dystonia severity. LY235959 had no effect on motor function when given alone and did not reduce the antiparkinsonian response to levodopa. These findings suggest that NMDA receptor blockade may ameliorate the dyskinetic complications of long-term levodopa therapy, without diminishing the beneficial effects on parkinsonian signs. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/8619541/Levodopa_induced_dyskinesias_improved_by_a_glutamate_antagonist_in_Parkinsonian_monkeys_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0364-5134&amp;date=1996&amp;volume=39&amp;issue=5&amp;spage=574 DB - PRIME DP - Unbound Medicine ER -