The NMDA receptor NR2B subtype selective antagonist Ro 25-6981 aggravates paroxysmal dyskinesia in the dt(sz) mutant.
Previously, enhanced levels of spermine which stimulates N-methyl-D-aspartate (NMDA) receptors, particularly those containing the NR2B subunit, were found in brains of dt(sz) mutant hamsters, a model of paroxysmal dyskinesia in which dystonic episodes occur in response to stress. Therefore, the effects of the NR2B selective NMDA receptor antagonist Ro 25-6981 ([R-(R,S)]-alpha-(4-hydroxyphenyl)-beta-methyl-4-phenyl-methyl)-1-piperidine-propanol] on severity of dystonia were investigated in the dt(sz) hamster. Ro 25-6981 failed to exert antidystonic effects, but even caused a moderate aggravation at higher doses (10.0, 12.5 mg/kg). This result indicates that overstimulation of receptors that include the NR2B subunit by polyamines is not involved in the dystonic syndrome. NR2B-selective NMDA receptor antagonists seem not to provide a novel approach in the treatment of hereditary paroxysmal dyskinesias.
Richter
Angelika
A
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine Hannover, Bünteweg 17, 30559, Hannover, Germany. rihtera@zedat.fu-Berlin.de
D000818:Animals; D002819:Chorea / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects; D009154:Mutation; D010636:Phenols / Q000009:adverse effects / Q000494:pharmacology*; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors
C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981