Prolongation of Levodopa Responses by GlycineB Antagonists in Parkinsonian Primates

• Authors: Stella M. Papa, Emory University; Yves P. Auberson, Novartis Institutes for Biomedical Research; J. Timothy Greenamyre, Emory University
• Journal Title: Annals of Neurology
• Volume: Volume 56, Number 5
• Publisher: Wiley: 12 months | 2004-11, Pages 723-727
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/ana.20279
• Subjects: Biology, Neuroscience

Abstract

To examine the antiparkinsonian effects of blocking glycineB receptors, we designed a pilot study testing the potent and selective antagonist, PAMQX, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates. PAMQX had no intrinsic effects but markedly potentiated the antiparkinsonian action of levodopa. In a dose-dependent fashion, coadministration of the glycineB antagonist with levodopa extended the response duration by nearly 60%. It is noteworthy that PAMQX, within a considerable dose range, did not cause ataxia or other side effects. These data indicate that blocking N-methyl-d-aspartate receptors selectively to manipulate dopaminergic-mediated motor responses may be produced effectively by glycineB antagonists.