The NR2B-selective NMDA receptor antagonist CP-101,606 exacerbates L-DOPA-induced dyskinesia and provides mild potentiation of anti-parkinsonian effects of L-DOPA in the MPTP-lesioned marmoset model of Parkinson's disease

The Pharmacology of l-DOPA-Induced Dyskinesia in Parkinson’s Disease

“…Thus, negative allosteric modulation of NMDA receptors with the NR2B antagonist Co-101,244/PD-174,494 alleviated LID in the MPTP-lesioned macaque . The results obtained with dual NR1/ NR2B antagonists are more difficult to interpret, as traxoprodil exerted a mild antidyskinetic effect in a phase II clinical trial , whereas it exacerbated dyskinesia severity in the MPTP-lesioned NHP (Nash et al, 2004). Likewise, dual blockade of the NR1A/2A subunits with MDL-100,453 exacerbated LID in the MPTP-lesioned NHP .…”

Unprecedented therapeutic potential with a combination of A2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson's disease

“…In particular, NR2B receptor antagonists have been proposed as promising alternatives for the treatment of the motor symptoms of PD [30][31][32] and have been shown to be effective in alleviating experimental parkinsonism in both rodent and non-human primate models of PD [33][34][35][36]. NR2B antagonists have been shown to potentiate the therapeutic effect of L-Dopa [34,37,38] and to be effective in reducing L-Dopa-induced dyskinesia [33,39]. In both rat and human brains, NR2B receptors are expressed throughout the brain, with high expression in the cortex, hippocampus, striatum, thalamus and olfactory bulb [31].…”

Reduction of l-DOPA-Induced Dyskinesia by the Selective Metabotropic Glutamate Receptor 5 Antagonist 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]pyridine in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Lesioned Macaque Model of Parkinson's Disease

“…More recently, changes in the synaptic recruitment of ␣-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid receptor subunits in L-DOPA-treated primates have been observed (Silverdale et al, 2010). Indeed, the potential of various ionotropic glutamate receptor antagonists as treatments for motor complications in PD has been explored in several animal models of PD (Marin et al, 1996;Blanchet et al, 1999;Nash et al, 2004;Bibbiani et al, 2005;Silverdale et al, 2005). Unfortunately, interventions targeting such receptors have, to date, been beset by problems of poor efficacy and tolerability and side effects in clinical studies Nutt et al, 2008).…”