Disease relevance of C14126

• Kynurenine hydroxylase inhibitors reduce ischemic brain damage: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61-8048) in models of focal or global brain ischemia [1].
• 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 [2].
• The kynurenine 3-hydroxylase inhibitor Ro 61-8048 improves dystonia in a genetic model of paroxysmal dyskinesia [2].

High impact information on C14126

• The administration of mNBA (400 mg/kg intraperitoneally) or Ro 61-8048 (40 mg/kg intraperitoneally) to gerbils with a dialysis probe in their dorsal hippocampus or to rats with a dialysis probe in their parietal cortex significantly increased kynurenic acid concentration in the dialysates [1].
• We have examined whether the kynurenine 3-hydroxylase inhibitor Ro 61-8048 increases extracellular (KYNA) sufficiently to control excessive NMDA receptor function [3].
• In a passive avoidance paradigm, the administration of the NMDA receptor antagonist MK-801 (0.1 mg/kg) reduced, while Ro 61-8048 (4-80 mg/kg) did not change the latency time of entering into the dark compartment on the recall trial [4].
• Furthermore, it seems hopeful to use kynurenine derivatives (e.g. 4-chloro-kynurenine) or enzyme inhibitors (e.g. Ro-61-8048) to ensure an increased kynurenic acid concentration in the central nervous system [5].
• To evaluate this hypothesis, we used a pharmacological tool, the kynurenine 3-hydroxylase inhibitor Ro 61-8048, which raises KYNA levels acutely [6].

Anatomical context of C14126

• Finally, in rats with permanent occlusion of the middle cerebral artery, mNBA (200-400 mg/kg i.p.) and Ro 61-8048 (40 mg/kg i.p.) administration reduced the infarct volume [7].

Associations of C14126 with other chemical compounds

• The neuroprotective effects of two kynurenine hydroxylase inhibitors, (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfona mide (Ro 61-8048), were studied in vitro and in vivo [7].

Gene context of C14126

• 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 [2].

References