Influence of atropine and pralidoxime on organophosphorus cholinesterase inhibitors-induced epileptic activity

• Project/Area Number: 23592675
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: NARIMATSU EICHI 札幌医科大学, 医学部, 教授 (70295343)
• Co-Investigator(Kenkyū-buntansha): NIIYA Tomohisa 札幌医科大学, 医学部, 講師 (80510312) ; KAWAMATA Mikito 信州大学, 医学部, 教授 (90315523) ; YAMAUCHI Masanori 東北大学, 医学(系)研究科(研究院), 教授 (00404723)
• Project Period (FY): 2011-04-28 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 有機リン / コリンエステラーゼ阻害薬 / てんかん / 海馬 / アトロピン / プラリドキシム / 抗痙攣薬 / 中毒 / 痙攣波 / 有機リン中毒 / パラオキソン

Outline of Final Research Achievements

We investigated the epilepsy-inducing actions of paraoxon with elevated [K+]e and the effects of atropine, pralidoxime, and selective muscarinic acetylcholine receptor (mAChR) antagonists on the actions of paragon.
paraoxon-induced cholinesterase inhibition elicited epileptic activity in elevated [K+]e but not normal [K+]e. Treatment for hyperkalemia likely prevents the development of epilepsy in organophosphate intoxication. Paraoxon-induced epileptic activity was inhibited by atropine but not by pralidoxime. Relatively weak mAChR activation likely elicited epileptic activity in 7.5 mM [K+]e. Atropine, rather than pralidoxime, may be effective at inhibiting organophosphate-induced epileptic activity.

Research Products

• [Journal Article] Blockers of adenosine A1, but not muscarinic acetylcholine, receptors improve excessive extracellular glutamate-induced synaptic depression. (2013)
  • Author(s): Narimatsu E, Niiya T, Takada Y, Takahashi K, Yamauchi M, Yamakage M
  • Journal Title: Neuroscience Research Volume: 75 Issue: 2 Pages: 103-111
  • DOI: 10.1016/j.neures.2012.11.002
  • Peer Reviewed
• [Journal Article] プラリドキシムはロクロニウム筋弛緩に対するパラオキソンの拮抗作用を時間依存性に抑制する (2012)
  • Author(s): 成松英智，新谷知久，高橋和伸，山内正憲， 山蔭道明
  • Journal Title: American Journal of Emergency Medicine Volume: Epub ahead of print
  • Peer Reviewed
• [Presentation] Elevation and suppression of paraoxon-induced epileptic activity in the rat hippocampus (2015)
  • Author(s): Yukimasa Takada, Narimatsu Eichi, Kazunobu Takahashi, Tomohisa Niiya, Michiaki Yamakage
  • Organizer: ANESTHESIOLOGY 2015
  • Place of Presentation: SAN DIEGO, USA
  • Year and Date: 2015-10-24
  • Int'l Joint Research
• [Presentation] Influence of adenosine on glutamate-induced neuronal damage in rat hipocampal slices (2012)
  • Author(s): Narimatsu E, Takada Y, Takahashi K, NIiya T, Yamauchi M, Yamakage M
  • Organizer: American Society of anesthesiology annual meeting 2012
  • Place of Presentation: Washington, D.C.
• [Presentation] 海馬グルタミン酸神経細胞損傷に対するコリンエステラーゼ阻害の影響 (2011)
  • Author(s): 成松英智，高橋和伸，高田幸昌，新谷知久，山内正憲， 山蔭道明
  • Organizer: 米国麻酔科学会 2011
  • Place of Presentation: Chicago, USA