Prolongation of levodopa responses by glycineB antagonists in parkinsonian primates

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.