The carbonic anhydrase inhibitor acetazolamide exerts antidystonic effects in the dt(sz) mutant hamster.
Previous studies suggested an involvement of gamma-aminobutyric acid (GABA)-mediated excitation by an enhanced efflux of bicarbonate ions in addition to retarded development of GABAergic inhibition in the syndrome of dt(sz) mutant hamsters, a model of paroxysmal dyskinesia in which dystonic episodes occur in response to stress. Acetazolamide blocks bicarbonate regeneration in neurons and can thereby reduce GABA-mediating excitation without affecting GABA-mediated inhibition. In the present study, the effects of acetazolamide (15-60 mg/kg, i.p.) on severity of dystonia were therefore examined in dt(sz) hamsters. Acetazolamide significantly reduced the severity of dystonia at a dose of 60 mg/kg. These data are in line with several case reports from patients with paroxysmal dystonia, suggesting that acetazolamide can be useful in the treatment of this movement disorder. The mechanism of the antidystonic efficacy of acetazolamide has to be examined by further studies.
Richter
Angelika
A
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, FU Berlin, Koserstrasse 20, 14195 Berlin, Germany. richtera@zedat.fu-berlin.de
Hamann
Melanie
M
D000086:Acetazolamide / Q000627:therapeutic use*; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004421:Dystonia / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation
D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide