Vécsei L, Miller J, MacGarvey U, Beal M F
Neurology Service, Massachusetts General Hospital, Boston 02114.
Brain Res Bull. 1992 Feb;28(2):233-8. doi: 10.1016/0361-9230(92)90184-y.
Kynurenine is a direct precursor of kynurenic acid, the only known endogenous antagonist of excitatory amino acid receptors in the brain. Kynurenine administered intraperitoneally (150, 450, 900 mg/kg) 2 h before pentylenetetrazol injection dose-dependently increased the time to seizures, the time to death and the survivorship of mice. Kynurenine dose-dependently increased the time to seizures and the time to death in mice with NMDLA-induced seizures. Kynurenine, 900 mg/kg, was equally efficacious to diazepam, 2 mg/kg. Probenecid dose-dependently increased the time to seizures, the time to death and the survivorship of mice with pentylenetetrazol-induced seizures. Probenecid had no significant effects on NMDLA-induced seizures, although the time to death was prolonged in the NMDLA 500 mg/kg group. Probenecid potentiated the effects of kynurenine in these tests. Both probenecid and kynurenine significantly increased kynurenine and kynurenic acid concentrations in mouse cerebral cortex and striatum. These findings suggest that kynurenine (metabolized to kynurenic acid) has anticonvulsant effects, and probenecid potentiates these effects in mice.
犬尿氨酸是犬尿酸的直接前体，犬尿酸是大脑中已知的唯一内源性兴奋性氨基酸受体拮抗剂。在注射戊四氮前2小时腹腔注射犬尿氨酸（150、450、900毫克/千克）可剂量依赖性地延长小鼠癫痫发作时间、死亡时间并提高其存活率。犬尿氨酸可剂量依赖性地延长N-甲基-D-天冬氨酸（NMDA）诱导癫痫发作小鼠的癫痫发作时间和死亡时间。900毫克/千克的犬尿氨酸与2毫克/千克的地西泮疗效相当。丙磺舒可剂量依赖性地延长戊四氮诱导癫痫发作小鼠的癫痫发作时间、死亡时间并提高其存活率。丙磺舒对NMDA诱导的癫痫发作无显著影响，尽管在500毫克/千克NMDA组中死亡时间有所延长。在这些试验中，丙磺舒增强了犬尿氨酸的作用。丙磺舒和犬尿氨酸均显著提高了小鼠大脑皮层和纹状体中犬尿氨酸和犬尿酸的浓度。这些发现表明，犬尿氨酸（代谢为犬尿酸）具有抗惊厥作用，丙磺舒可增强小鼠的这些作用。
