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.
Kreil
Annette
A
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität (FU) Berlin, Koserstr. 20, D-14195 Berlin, Germany.
Richter
Angelika
A
D000818:Animals; D006224:Cricetinae; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004421:Dystonia / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D018756:GABA Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D009154:Mutation; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D010091:Oximes / Q000008:administration & dosage / Q000627:therapeutic use; D011897:Random Allocation; D012720:Severity of Illness Index; D000078308:Tiagabine; D013997:Time Factors; D016896:Treatment Outcome
D018756:GABA Antagonists; D009557:Nipecotic Acids; D010091:Oximes; C078793:NNC 711; C030278:nipecotic acid; D000078308:Tiagabine