Sakurada Koichi, Ohta Hikoto
Department of Forensic Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Toxicology Section, Department of Forensic Chemistry, National Research Institute of Police Science, 6-3-1 Kashiwanoha, Kashiwa, Chiba 277-0882, Japan.
Leg Med (Tokyo). 2020 Nov;47:101761. doi: 10.1016/j.legalmed.2020.101761. Epub 2020 Jul 15.
On the battlefields of Syria, many innocent civilians have been killed or injured by sarin poisoning. In Malaysia in February 2017, a North Korean man was assassinated with VX at Kuala Lumpur International Airport. In the face of such threats, a more effective antidote against organophosphonate acetylcholinesterase (AChE) inhibitors is needed, one that can freely penetrate into the central nervous system (CNS) through the blood-brain barrier (BBB). In the 1995 Tokyo subway sarin attack, which produced more than 6,000 victims, 2-pyridinealdoxime methiodide was the most commonly used antidote in hospitals, but it was unable to prevent CNS damage and no other oximes have been approved for use in Japan. Ultimately, 12 people died, and many victims had severe neurological injuries or sequelae. Although more than 25 years have passed since the incident, progress has been slow in the development of a new antidote that can penetrate the BBB, restore AChE activity in the CNS, and definitely prevent brain injury. From the perspectives of countering terrorism and protecting innocent people from nerve agent attacks, the search for nerve agent antidotes should be accelerated with the goals of improving both survival and quality of life. This review gives an overview of a series of our studies on the development of a new antidote since the Tokyo subway sarin attack and emphasizes that there is unfortunately still no promising antidote for saving the CNS in Japan.
在叙利亚战场上，许多无辜平民因沙林中毒而伤亡。2017年2月在马来西亚，一名朝鲜男子在吉隆坡国际机场被VX毒剂暗杀。面对此类威胁，需要一种更有效的抗有机磷酸酯类乙酰胆碱酯酶（AChE）抑制剂的解毒剂，一种能够通过血脑屏障（BBB）自由穿透进入中枢神经系统（CNS）的解毒剂。在1995年造成6000多名受害者的东京地铁沙林袭击事件中，2-吡啶醛肟甲基碘化物是医院最常用的解毒剂，但它无法预防中枢神经系统损伤，且日本尚未批准其他肟类药物用于解毒。最终，12人死亡，许多受害者有严重的神经损伤或后遗症。尽管该事件已过去25年多，但能够穿透血脑屏障、恢复中枢神经系统中AChE活性并切实预防脑损伤的新型解毒剂的研发进展缓慢。从反恐以及保护无辜民众免受神经毒剂袭击的角度来看，应加快寻找神经毒剂解毒剂，目标是提高生存率和生活质量。本综述概述了自东京地铁沙林袭击事件以来我们在新型解毒剂研发方面的一系列研究，并强调遗憾的是，在日本仍没有有望挽救中枢神经系统的解毒剂。
