The Kynurenine 3-hydroxylase Inhibitor Ro 61-8048 Improves Dystonia in a Genetic Model of Paroxysmal Dyskinesia

Angelika Richter, Melanie Hamann

Eur J Pharmacol. 2003 Sep 30;478(1):47-52.

PMID: 14555184

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP199666030	Ro 61-8048		199666-03-0	Price