Effects of a NR2B selective NMDA glutamate antagonist, CP-101,606, on dyskinesia and Parkinsonism.
Glutamate antagonists decrease dyskinesia and augment the antiparkinsonian effects of levodopa in animal models of Parkinson's disease (PD). In a randomized, double-blind, placebo-controlled clinical trial, we investigated the acute effects of placebo and two doses of a NR2B subunit selective NMDA glutamate antagonist, CP-101,606, on the response to 2-hour levodopa infusions in 12 PD subjects with motor fluctuations and dyskinesia. Both doses of CP-101,606 reduced the maximum severity of levodopa-induced dyskinesia approximately 30% but neither dose improved Parkinsonism. CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects.
Nutt
John G
JG
Department of Neurology, Oregon Health and Science University, Portland, Oregon 97201, USA. nuttj@ohsu.edu
Gunzler
Steven A
SA
Kirchhoff
Trish
T
Hogarth
Penelope
P
Weaver
Jerry L
JL
Krams
Michael
M
Jamerson
Brenda
B
Menniti
Frank S
FS
Landen
Jaren W
JW