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

Exp Neurol. 2004 Aug;188(2):471-9. doi: 10.1016/j.expneurol.2004.05.004.


In Parkinson's disease (PD), degeneration of the dopaminergic nigrostriatal pathway leads to enhanced transmission at NMDA receptors containing NR2B subunits. Previous studies have shown that some, but not all, NR2B-containing NMDA receptor antagonists alleviate parkinsonian symptoms in animal models of PD. Furthermore, enhanced NMDA receptor-mediated transmission underlies the generation of L-DOPA-induced dyskinesia (LID). The subunit content of NMDA receptors responsible for LID is not clear. Here, we assess the actions of the NMDA antagonist CP-101,606 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmoset model of Parkinson's disease. CP-101,606 is selective for NMDA receptors containing NR2B subunits, with higher affinity for NR1/NR2B complexes compared to ternary NR1/NR2A/NR2B complexes. CP-101,606 had no significant effect on parkinsonian symptoms when administered as monotherapy over a range of doses (0.1-10 mg/kg). CP-101,606 provided a modest potentiation of the anti-parkinsonian actions of L-DOPA (8 mg/kg), although, at doses of 1 and 3 mg/kg, CP-101,606 exacerbated LID. Results of this study provide further evidence of differences in the anti-parkinsonian activity and effects on LID of the NR2B subunit selective NMDA receptor antagonists. These distinctions may reflect disparities in action on NR1/NR2B as opposed to NR1/NR2A/NR2B receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Callithrix
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Dyskinesia, Drug-Induced / physiopathology*
  • Female
  • Levodopa / adverse effects*
  • Levodopa / therapeutic use
  • Male
  • Motor Activity / drug effects
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / physiopathology*
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Range of Motion, Articular / drug effects
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Treatment Failure


  • NR2B NMDA receptor
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • Levodopa
  • traxoprodil mesylate