Ro 61-8048 is an orally active and selective inhibitor of kynurenine 3-hydroxylase, with an IC50 of 37 nM. Ro 61-8048 provokes a significant increase of extracellular kynurenic acid concentrations[1].
体外研究 (In Vitro)
In gerbils, a dose of 30 µmol/kg po (12.64 µg/kg Ro 61-8048, compound 16) leads to inhibition of the cerebral enzyme which peaked after 2h (∼85% inhibition) and persisted for up to 8 h[1]. Ro 61-8048 (0.1-100 μM) strongly reduces QUIN neo-formation, suggesting that, in vitro, kynurenine hydroxylase activity is required for QUIN neosynthesis[3].
体内研究 (In Vivo)
Ro 61-8048 (50, 100 and 150 mg/kg i.p.) significantly reduces the severity of dystonia in dtsz hamsters without leading to marked central side effects[2]. Ro 61-8048 (100 mg/kg i.p.) provokes a two- to threefold increase of the endogeneous broad spectrum glutamate receptor antagonist kynurenic acid in the striatum, cerebellum and brainstem of mutant hamsters[2].