Fachbereich Veterinärmedizin


Service-Navigation

    Publikationsdatenbank

    The kynurenine 3-hydroxylase inhibitor Ro 61-8048 improves dystonia in a genetic model of paroxysmal dyskinesia (2003)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Richter, Angelika
    Hamann, Melanie
    Quelle
    European journal of pharmacology; 478(1) — S. 47–52
    ISSN: 0014-2999
    Sprache
    Englisch
    Verweise
    Pubmed: 14555184
    Kontakt
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    Tel.+49 30 838 53221 Fax.+49 30 838 53112
    email:pharmakologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    The effects of the novel kynurenine 3-hydroxylase inhibitor 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide (Ro 61-8048) on severity of dystonia were examined in dt(sz) mutant hamsters, an animal model of paroxysmal dystonia, in which stress precipitates dystonic episodes. Ro 61-8048 (50, 100 and 150 mg/kg i.p.) significantly reduced the severity of dystonia in dt(sz) hamsters without leading to marked central side effects. Determinations of kynurenic acid concentrations in brain homogenates demonstrated that Ro 61-8048 (100 mg/kg i.p.) provoked a two- to threefold increase of the endogeneous broad spectrum glutamate receptor antagonist kynurenic acid in the striatum, cerebellum and brainstem of mutant hamsters. The antidystonic efficacy of Ro 61-8048 at well-tolerated doses suggests that kynurenine 3-hydroxylase inhibitors should be considered as new therapeutic candidates for the treatment of dyskinesias.