Effects of the kynurenine 3-hydroxylase inhibitor Ro 61-8048 after intrastriatal injections on the severity of dystonia in the dt sz mutant.
Striatal dysfunctions seem to play a key role in the pathophysiology of dystonia in the dt(sz) mutant hamster, a model of paroxysmal non-kinesigenic dyskinesia, in which stress precipitates dystonic episodes. Previous examinations have shown changes in kynurenic acid levels and antidystonic effects of the kynurenine 3-hydroxylase inhibitor 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfon-amide (Ro 61-8048) after systemic treatment in dt(sz) hamsters. In the present study, intrastriatal injections of Ro 61-8048 (60-80 microg/hemisphere) significantly reduced the severity of dystonia in dt(sz) hamsters, suggesting that kynurenine 3-hydroxylase inhibitors may be interesting candidates for managing dyskinesias which are related to striatal dysfunction.
Hamann
Melanie
M
Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, 14195 Berlin, Germany.
Sander
Svenja E
SE
Richter
Angelika
A
D000818:Animals; D006224:Cricetinae; D004421:Dystonia / Q000188:drug therapy* / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D050601:Kynurenine 3-Monooxygenase / Q000037:antagonists & inhibitors*; D008845:Microinjections; D009154:Mutation / Q000502:physiology; D017072:Neostriatum / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D004791:Enzyme Inhibitors; C110196:Ro 61-8048; D013449:Sulfonamides; D013844:Thiazoles; D050601:Kynurenine 3-Monooxygenase