PMID- 19680820
OWN - NLM
STAT- MEDLINE
DCOM- 20100421
LR  - 20211020
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 40
IP  - 1-2
DP  - 2010 Jan
TI  - Treatment with tertiary oximes prevents seizures and improves survival following 
      sarin intoxication.
PG  - 63-9
LID - 10.1007/s12031-009-9259-7 [doi]
AB  - The capability of the tertiary oximes, monoisonitrosoacetone (MINA) and 
      diacetylmonoxime (DAM), to reactivate acetylcholinesterase (AChE) inhibited by 
      sarin (GB) in the blood, brain, and peripheral tissues of guinea pigs was 
      compared with that of the quaternary oximes 2-PAM, HLo7, and MMB-4. Animals were 
      injected subcutaneously (s.c.) with 1.0 x LD(50) of GB and treated 
      intramuscularly (i.m.) 5 min later with one of these oximes. Sixty minutes after 
      GB exposure, tissues were collected for AChE analysis. At low doses, MINA and DAM 
      produced significant increases in AChE activity in all brain areas examined, but 
      no significant AChE reactivation in peripheral tissues or blood. At higher doses, 
      MINA and DAM increased AChE activity in the brain, peripheral tissues, and blood. 
      In contrast, the quaternary oximes produced significant reactivation in 
      peripheral tissues and blood AChE, but no significant reactivation of brain AChE. 
      In another study, animals were pretreated i.m. with pyridostigmine 30 min prior 
      to s.c. challenge with 2.0 x LD(50) of GB and treated i.m. 1 min later with 
      atropine sulfate (2.0 mg/kg), plus a varied dose of oximes. MINA and DAM 
      prevented or terminated GB-induced seizure activity and protected against GB 
      lethality in a dose-dependent fashion. In contrast, none of the quaternary oximes 
      prevented or stopped GB-induced seizures. Thus, tertiary oximes reactivated AChE 
      in the brain, improved survival, and terminated seizures following GB 
      intoxication.
FAU - Shih, Tsung-Ming
AU  - Shih TM
AD  - Pharmacology Branch, Research Division, U.S. Army Medical Research Institute of 
      Chemical Defense, ATTN: MCMR-CDR-P, Aberdeen Proving Ground, MD 21010-5400, USA. 
      tsungming.a.shih@us.army.mil
FAU - Skovira, Jacob W
AU  - Skovira JW
FAU - O'Donnell, John C
AU  - O'Donnell JC
FAU - McDonough, John H
AU  - McDonough JH
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090813
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Cholinesterase Reactivators)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Oximes)
RN  - 0 (Pralidoxime Compounds)
RN  - 0 (Pyridinium Compounds)
RN  - 120103-35-7 (HLo 7)
RN  - 19SQ93LM6H (diacetylmonoxime)
RN  - 61444-84-6 (N,N'-monomethylenebis(pyridiniumaldoxime))
RN  - 7C0697DR9I (Atropine)
RN  - B4XG72QGFM (Sarin)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - K324J5K4HM (Diacetyl)
RN  - KVI301NA53 (Pyridostigmine Bromide)
RN  - P7MU9UTP52 (pralidoxime)
SB  - IM
MH  - Acetylcholinesterase/blood/drug effects
MH  - Animals
MH  - Atropine/pharmacology
MH  - Brain/*drug effects/physiopathology
MH  - Cholinesterase Inhibitors/toxicity
MH  - Cholinesterase Reactivators/*pharmacology/therapeutic use
MH  - Diacetyl/analogs & derivatives/pharmacology/therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions/physiology
MH  - Enzyme Activation/drug effects/physiology
MH  - Guinea Pigs
MH  - Injections, Intramuscular
MH  - Male
MH  - Muscarinic Antagonists/pharmacology
MH  - Oximes/*pharmacology/therapeutic use
MH  - Pralidoxime Compounds/pharmacology/therapeutic use
MH  - Pyridinium Compounds/pharmacology/therapeutic use
MH  - Pyridostigmine Bromide/pharmacology
MH  - Sarin/*toxicity
MH  - Seizures/*chemically induced/*drug therapy/physiopathology
MH  - Treatment Outcome
MH  - Up-Regulation/drug effects/physiology
EDAT- 2009/08/15 09:00
MHDA- 2010/04/22 06:00
CRDT- 2009/08/15 09:00
PHST- 2009/07/06 00:00 [received]
PHST- 2009/07/20 00:00 [accepted]
PHST- 2009/08/15 09:00 [entrez]
PHST- 2009/08/15 09:00 [pubmed]
PHST- 2010/04/22 06:00 [medline]
AID - 10.1007/s12031-009-9259-7 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2010 Jan;40(1-2):63-9. doi: 10.1007/s12031-009-9259-7. Epub 2009 
      Aug 13.