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

Abstract

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.

• Authors: Annette Kreil, Angelika Richter
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 521 Issue 1-3 Pg. 95-8 (Oct 03 2005) ISSN: 0014-2999 [Print] Netherlands
• PMID: 16183056 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GABA Antagonists
• Nipecotic Acids
• Oximes
• NNC 711
• nipecotic acid
• Tiagabine

Topics

• Animals
• Cricetinae
• Disease Progression
• Dose-Response Relationship, Drug
• Dystonia (genetics, pathology, prevention & control)
• Female
• GABA Antagonists (administration & dosage, therapeutic use)
• Injections, Intraperitoneal
• Male
• Mutation
• Nipecotic Acids (administration & dosage, therapeutic use)
• Oximes (administration & dosage, therapeutic use)
• Random Allocation
• Severity of Illness Index
• Tiagabine
• Time Factors
• Treatment Outcome