Pharmacology Branch, Research Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USA.
Drug Chem Toxicol. 2010 Jul;33(3):279-83. doi: 10.3109/01480540903483417.
Near-lethal exposure to nerve agents produces prolonged epileptiform seizures requiring the administration of benzodiazepine anticonvulsant drugs, such as diazepam. Clinically, benzodiazepines are reported to lose anticonvulsant effectiveness the greater the delay between seizure onset and benzodiazepine treatment. This time-dependent diminished effectiveness of diazepam was tested in the present study. Seizures elicited by the nerve agent, soman, were produced in guinea pigs instrumented to record brain electrocorticographic (ECoG) activity. Different groups of animals were administered 10 mg/kg, intramuscularly, of diazepam at 5, 40, 60, 80, or 160 minutes after the onset of seizure activity. There was a progressive loss in the anticonvulsant efficacy of diazepam as the treatment was delayed after seizure onset, but no differences in the time for diazepam to stop seizures. The results show a diminished ability of diazepam to stop nerve-agent-induced seizures the longer treatment is delayed.
接近致死剂量的神经毒剂暴露会导致长时间的癫痫样发作，需要使用苯二氮䓬类抗惊厥药物，如地西泮。临床上，据报道，苯二氮䓬类药物的抗惊厥作用会随着发作开始和苯二氮䓬类药物治疗之间的延迟时间增加而降低。本研究测试了地西泮的这种时间依赖性有效性降低。通过给已安装记录脑皮层电图（ECoG）活动仪器的豚鼠注射神经毒剂梭曼来诱发癫痫发作。不同组别的动物在癫痫发作开始后 5、40、60、80 或 160 分钟时，肌肉内注射 10mg/kg 的地西泮。随着癫痫发作开始后治疗的延迟，地西泮的抗惊厥疗效逐渐降低，但地西泮停止癫痫发作的时间没有差异。结果表明，地西泮阻止神经毒剂引起的癫痫发作的能力随着治疗延迟而降低。
