NDLI: Treatment with Tertiary Oximes Prevents Seizures and Improves Survival Following Sarin Intoxication

Content Provider	Springer Nature Link
Author	Shih, Tsung Ming Skovira, Jacob W. O’Donnell, John C. McDough, John H.
Copyright Year	2009
Abstract	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, HLö7, and MMB-4. Animals were injected subcutaneously (s.c.) with 1.0 × 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 × 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.
Starting Page	63
Ending Page	69
Page Count	7
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	40
Issue Number	1-2
e-ISSN	15591166
Language	English
Publisher	Humana Press Inc
Publisher Date	2009-08-13
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Sarin Acetylcholinesterase Oxime reactivator Tertiary oxime Anticonvulsant Seizures Neurology Neurosciences
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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