The NMDA receptor NR2B subtype selective antagonist Ro 25-6981 aggravates paroxysmal dyskinesia in the dt sz mutant

Abstract

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)]-α-(4-hydroxyphenyl)-β-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.