摘要
背景:神经毒性化学战剂可被归类为对人类最危险的化学物质。这些药物中最有效的是能够限制乙酰胆碱酯酶(AChE)的有机磷酸酯(OPs),而乙酰胆碱酯酶(AChE)则控制神经冲动的传递。当AChE被OPs抑制时,其重新活化通常可以通过阳离子肟来进行。然而,直到今天,还没有开发出一种通用的防御剂,其对AChE的完全有效的再活化活性被许多现有的神经毒性OPs所抑制。因此,在治疗被OPs所致毒的人之前,有必要确定用于污染的神经毒性化合物,以便选择最有效的肟。不幸的是,该任务通常需要相对较长的时间,从而增加了死亡的可能性。阳离子肟也表现出有限的渗透血脑屏障(BBB)的能力。这一事实损害了他们重新激活神经系统内部AChE的能力。 方法:我们对当今科学文献中有关OPs的数据进行了全面搜索,以涵盖开发针对这些化合物的有效解毒剂的研究仍面临的所有主要弊端。 结果:因此,本篇有关神经毒性OPs和AChE激活的评论为新药的开发提供了见识。最期待的防御剂是一种无毒性的分子,可以有效地激活被所有神经毒性OPs抑制的AChE。 结论:要开发这些新试剂,应应用各种科学研究领域,尤其是理论程序,如计算科学(计算机模拟,对接和动力学),有机合成,光谱学方法,生物学,生化和生物物理信息,药物化学,药理学和毒理学,是必要的。
关键词: 乙酰胆碱酯酶,活化剂,神经毒性有机磷化合物,肟,作战剂,化学防御作用。
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