Doebler J A, Wall T J, Martin L J, Shih T M, Anthony A
Life Sci. 1985 Mar 18;36(11):1107-15. doi: 10.1016/0024-3205(85)90496-5.
Studies were conducted to determine effects of the benzodiazepine anticonvulsant diazepam on soman induced brain neuronal RNA depletion and lethality in rats. Quantitative azure B-RNA cytophotometry was used to monitor RNA responses of cerebrocortical (layer V) and striatal neurons following dosages of 0.5, 0.9 and 1.5 LD50 soman (LD50 = 135 micrograms/kg, sc), whereas mean time of death and 24-h survival following 0.8, 1.2 and 1.5 LD50 were used to assess the antidotal efficacy of diazepam (2.2 mg/kg, im) pretreatment. Soman produced dose-dependent RNA depletion in both brain regions. This RNA impairment was almost completely prevented by diazepam, although neuronal RNA contents were generally slightly lower than corresponding control values. However, diazepam pretreatment was not associated with any change in mean time of death or in 24-h survival. The overall data suggest that excessive neural activity per se may underlie the genesis of soman-induced central metabolic impairments, but also appear to effectively dissociate epileptiform activity from lethal actions of soman.
开展了多项研究，以确定苯二氮䓬类抗惊厥药地西泮对大鼠体内梭曼诱导的脑神经元RNA耗竭及致死率的影响。采用定量天青B-RNA细胞光度法监测给予0.5、0.9和1.5倍半数致死量梭曼（半数致死量=135微克/千克，皮下注射）后大脑皮质（第V层）和纹状体神经元的RNA反应，而给予0.8、1.2和1.5倍半数致死量梭曼后，用平均死亡时间和24小时存活率评估地西泮（2.2毫克/千克，肌肉注射）预处理的解毒效果。梭曼在两个脑区均产生剂量依赖性RNA耗竭。尽管神经元RNA含量通常略低于相应的对照值，但地西泮几乎完全预防了这种RNA损伤。然而，地西泮预处理与平均死亡时间或24小时存活率的任何变化均无关。总体数据表明，过度的神经活动本身可能是梭曼诱导的中枢代谢损伤发生的基础，但似乎也有效地将癫痫样活动与梭曼的致死作用分离。
