Antidystonic efficacy of gamma-aminobutyric acid uptake inhibitors in the dtsz mutant.

In the dtsz mutant hamster, a model of paroxysmal dyskinesia in which dystonic episodes occur in response to stress, previous studies suggested that retarded development of gamma-aminobutyric acid (GABA)ergic inhibition plays a critical role in the pathogenesis. In the present study, we therefore examined the effects of selective GABA uptake inhibitors on severity of dystonia in dtsz hamsters. R(-)N-(4,4-di(3-methylthien-2-yl)-but-3-enyl) nipecotic acid hydrochloride (tiagabine, 5-20 mg/kg i.p.) and 1-[2-[[(diphenylmethylene) imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (NNC-711, 1-10 mg/kg i.p.) significantly reduced the severity of dystonia. These data suggest that GABA uptake inhibitors may provide novel therapeutic approaches for paroxysmal dyskinesias.