PMID- 17096183
OWN - NLM
STAT- MEDLINE
DCOM- 20070201
LR  - 20220716
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 23
IP  - 12
DP  - 2006 Dec
TI  - 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.
PG  - 2827-33
AB  - 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.
FAU - Ohta, Hikoto
AU  - Ohta H
AD  - Toxicology Section, Department of Forensic Chemistry, National Research Institute 
      of Police Science, Kashiwa, Chiba, 277-0882, Japan. ohta@nrips.go.jp
FAU - Ohmori, Takeshi
AU  - Ohmori T
FAU - Suzuki, Shinichi
AU  - Suzuki S
FAU - Ikegaya, Hiroshi
AU  - Ikegaya H
FAU - Sakurada, Koichi
AU  - Sakurada K
FAU - Takatori, Takehiko
AU  - Takatori T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061110
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Antidotes)
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Cholinesterase Reactivators)
RN  - 0 (Indicators and Reagents)
RN  - B4XG72QGFM (Sarin)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase/*blood
MH  - Antidotes/*pharmacology
MH  - Chemical Warfare Agents/*pharmacology
MH  - Cholinesterase Inhibitors/blood/*pharmacology
MH  - Cholinesterase Reactivators/*pharmacology
MH  - Drug Evaluation, Preclinical
MH  - Erythrocytes/*drug effects/*enzymology
MH  - Humans
MH  - Indicators and Reagents
MH  - Magnetic Resonance Spectroscopy
MH  - Sarin/*analogs & derivatives/blood/*pharmacology
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Structure-Activity Relationship
EDAT- 2006/11/11 09:00
MHDA- 2007/02/03 09:00
CRDT- 2006/11/11 09:00
PHST- 2006/05/31 00:00 [received]
PHST- 2006/07/14 00:00 [accepted]
PHST- 2006/11/11 09:00 [pubmed]
PHST- 2007/02/03 09:00 [medline]
PHST- 2006/11/11 09:00 [entrez]
AID - 10.1007/s11095-006-9123-1 [doi]
PST - ppublish
SO  - Pharm Res. 2006 Dec;23(12):2827-33. doi: 10.1007/s11095-006-9123-1. Epub 2006 Nov 
      10.