2010 Fiscal Year Final Research Report

Study of effects of novel PAM analogues on the treatment of poisoning by nerve agents

Research Project

Project/Area Number	20592133
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Emergency medicine
Research Institution	National Research Institute of Police Science
Principal Investigator	SAKURADA Koichi 科学警察研究所, 法科学第一部, 室長 (10334228)
Project Period (FY)	2008 – 2010
Keywords	神経ガス / オキシム / パム / 2-PAM / 4-PAO / BBB
Research Abstract	A liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was validated and applied to the in vitro determination of novel PAM-type oximes, which can penetrate the blood-brain barrier(BBB) and reactivate acetylcholinesterase(AChE) inhibited by alkylphosphonate in various organs. It was indicated that the LC-MS/MS method could be a reliable method with high precision and accuracy for quantification of PAM-type oximes in various biological samples. On the other hand, although the oximes are potential antidotes to poisonings that inhibit AChE, but they are also toxic. To investigate the mechanism of their toxicity, the effects of oximes on the enzymes choline oxidase(ChOD) and cytochrome c oxidase(CyCOD) of the respiratory chain in mitochondria were examined. The results showed that the toxicities of oximes might be related to their inactivation of mitochondrial oxidase enzymes and generation of reactive oxygen species.