Health & Environmental Research Online (HERO)


Print Feedback Export to File
1617361 
Journal Article 
New safe method for preparation of sarin-exposed human erythrocytes acetylcholinesterase using non-toxic and stable sarin analogue isopropyl p-nitrophenyl methylphosphonate and its application to evaluation of nerve agent antidotes 
Ohta, H; Ohmori, T; Suzuki, S; Ikegaya, H; Sakurada, K; Takatori, T 
2006 
1 
Pharmaceutical Research
ISSN: 0724-8741
EISSN: 1573-904X 
23 
12 
2827-2833 
English 
17096183 
WOS:000242439700011 
INTRODUCTION: A non-toxic and stable sarin analogue, isopropyl p-nitrophenyl methylphosphonate (INMP), was synthesized for safe preparation of sarin-exposed acetylcholinesterase (AChE).

RESULTS AND DISCUSSION: This agent was stable for years, able to be handled in an ordinary laboratory without special care, and its 50% inhibitory concentration (IC50) on 0.04 U/ml human erythrocytes AChE was 15 nM. This reagent was thought to be especially useful since it enables experiments that require sarin-inhibited AChE, such as the development of antidotes for sarin, in a usual laboratory. To demonstrate the usefulness of this method, 40 known and novel pyridinealdoxime methiodide (PAM)-type oxime antidotes were synthesized, and their reactivation activities to INMP-exposed AChE and structure-activities correlation were studied.

CONCLUSION: Among the antidotes tested in this experiment except for 2-PAM, the compound found to have the highest reactivation activity, was the novel hydrophobic 2-PAM-type compound, 2-[(hydroxyimino)methyl]-1-[4-(tert-butyl)benzyl] pyridinium bromide. 
acetylcholinesterase; antidote; isopropyl p-nitrophenyl methylphosphonate (INMP); PAM; sarin