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Investigation of the toxic mechanism of oximes which are used in the treatment of poisoning by nerve agents

Research Project

Project/Area Number 23592690
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionNational 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)

Research Collaborator OHTA Hikoto  科学警察研究所, 法科学第三部, 室長 (40392261)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords4-PAO / 2-PAM / cardiac effect / ECG / actomyosin / ATPase / 神経ガス / オキシム / パム
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.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (4 results)

All 2014 2012

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (2 results) (of which Invited: 1 results)

  • [Journal Article] Lipophilicity indices derived from the liquid chromatographic behavior observed under bimodal retention conditions (reversed phase/hydrophilic interaction): Application to a representative set of pyridinium oximes2014

    • Author(s)
      Victor Voicu, Costel Sârbu, Florentin Tache, Florina Micăle,Ştefan F. Rădulescu, Koichi Sakurada, Hikoto Ohta, Andrei Medvedovici
    • Journal Title

      Talanta

      Volume: Vol.122 Pages: 172-179

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lipophilicity indices derived from the liquid chromatographic behavior observed under bimodal retention conditions (reversed phase/hydrophilic interaction): Application to a representative set of pyridinium oximes2014

    • Author(s)
      Victor Voicu, Costel Sarbu, Florentin Tache, Florina Micale, Stefan Flavian Radulescu, Koichi sakurada, Hikoto Ohta, Andrei Medvedovici
    • Journal Title

      Talanta

      Volume: 122 Pages: 172-179

    • DOI

      10.1016/j.talanta.2014.01.048

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Development of BBB-penetrative antidotes for reactivation of inhibited AChE in nerve agent poisoning2012

    • Author(s)
      Hikoto Ohta and Koichi Sakurada
    • Organizer
      13^<th> International Congress of the Romanian Society of Pharmacology, Therapeutics and Clinical Toxicology
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of BBB-penetrative antidotes for reactivation of inhibited AChE in nerve agent poisoning2012

    • Author(s)
      Hikoto Ohta and Koichi Sakurada
    • Organizer
      2012 International Congress of the Romanian Society of Pharmacology, Therapeutics and Clinical Toxicology
    • Place of Presentation
      Bucharest in Romania
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2011-08-05   Modified: 2019-07-29  

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