2013 Fiscal Year Final Research Report
Investigation of the toxic mechanism of oximes which are used in the treatment of poisoning by nerve agents
| Project/Area Number |
23592690
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | National Research Institute of Police Science |
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Principal Investigator |
SAKURADA Koichi 科学警察研究所, 法科学第一部, 室長 (10334228)
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| Research Collaborator |
OHTA Hikoto 科学警察研究所, 法科学第三部, 室長 (40392261)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 4-PAO / 2-PAM / cardiac effect / ECG / actomyosin / ATPase |
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| Research Abstract |
The pyridinium aldoxime methiodide (PAM)-type oxime 4-PAO, which can reactivate AChE inhibited by alkylphosphonate and penetrate the blood-brain barrier, is expected to be effective for reactivating blocked cholinesterase in the brain. However, the toxicity of 4-PAO has not yet been investigated in detail. The present study investigated the effects of 4-PAO on the contractile activity of the rat heart using electrocardiography analysis. 4-PAO was suggested to inhibit the atrioventricular conduction system more strongly than 2-PAM. In addition, not only 4-PAO but also 2-PAM inhibited the inherent K+-EDTA-ATPase catalytic activity of myosin, indicating that oximes might interact directly with the catalytic center of the myosin molecule. No significant inhibition was observed for less than 4uM 4-PAO, 2-PAM, 4-PAPE, obidoxime and DAM, which correspond to the clinical dose of 2-PAM. Further studies are required to clarify the mechanism of 4-PAO toxicity.
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