Treatment with tertiary oximes prevents seizures and improves survival following sarin intoxication.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Shih TM;Shih TM; Skovira JW; O'Donnell JC; McDonough JH
  • Source:
    Journal of molecular neuroscience : MN [J Mol Neurosci] 2010 Jan; Vol. 40 (1-2), pp. 63-9. Date of Electronic Publication: 2009 Aug 13.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Humana Press Country of Publication: United States NLM ID: 9002991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1166 (Electronic) Linking ISSN: 08958696 NLM ISO Abbreviation: J Mol Neurosci Subsets: MEDLINE
    • Publication Information:
      Publication: Totowa, NJ : Humana Press
      Original Publication: Boston : Birkhäuser [i.e. Cambridge, MA : Birkhäuser Boston, c1989-
    • Subject Terms:
      Brain/*drug effects ; Cholinesterase Reactivators/*pharmacology ; Oximes/*pharmacology ; Sarin/*toxicity ; Seizures/*chemically induced ; Seizures/*drug therapy; Acetylcholinesterase/blood ; Acetylcholinesterase/drug effects ; Animals ; Atropine/pharmacology ; Brain/physiopathology ; Cholinesterase Inhibitors/toxicity ; Cholinesterase Reactivators/therapeutic use ; Diacetyl/analogs & derivatives ; Diacetyl/pharmacology ; Diacetyl/therapeutic use ; Dose-Response Relationship, Drug ; Drug Interactions/physiology ; Enzyme Activation/drug effects ; Enzyme Activation/physiology ; Guinea Pigs ; Injections, Intramuscular ; Male ; Muscarinic Antagonists/pharmacology ; Oximes/therapeutic use ; Pralidoxime Compounds/pharmacology ; Pralidoxime Compounds/therapeutic use ; Pyridinium Compounds/pharmacology ; Pyridinium Compounds/therapeutic use ; Pyridostigmine Bromide/pharmacology ; Seizures/physiopathology ; Treatment Outcome ; Up-Regulation/drug effects ; Up-Regulation/physiology
    • 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 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.
    • References:
      Br J Pharmacol Chemother. 1957 Sep;12(3):340-3. (PMID: 13460241)
      J Pharm Pharmacol. 1979 May;31(5):295-9. (PMID: 37298)
      Brain Res Bull. 1990 Mar;24(3):429-36. (PMID: 2337822)
      Science. 1951 Nov 16;114(2968):524-5. (PMID: 14892783)
      Biochim Biophys Acta. 1959 Aug;34:555-7. (PMID: 14425589)
      Br J Pharmacol Chemother. 1958 Dec;13(4):399-403. (PMID: 13618543)
      Neurotoxicology. 2002 Sep;23(3):341-9. (PMID: 12387361)
      Chem Biol Interact. 2005 Dec 15;157-158:293-303. (PMID: 16256093)
      Biochim Biophys Acta. 1955 Sep;18(1):168-70. (PMID: 13260275)
      Neurotoxicol Teratol. 1988 Jul-Aug;10(4):287-94. (PMID: 3226371)
      Neurotoxicology. 1998 Jun;19(3):381-91. (PMID: 9621344)
      Life Sci. 1985 Sep 2;37(9):793-8. (PMID: 4033355)
      J Pharmacol Exp Ther. 1957 Apr;119(4):522-31. (PMID: 13429460)
      J Pharmacol Exp Ther. 2007 Jan;320(1):154-61. (PMID: 17015638)
      Eur J Pharm Sci. 2000 Jan;9(3):259-63. (PMID: 10594382)
      JAMA. 1989 Aug 4;262(5):649-52. (PMID: 2664236)
      Acta Physiol Pharmacol Neerl. 1960 Jul;9:276-302. (PMID: 13694367)
    • Accession Number:
      0 (Cholinesterase Inhibitors)
      0 (Cholinesterase Reactivators)
      0 (Muscarinic Antagonists)
      0 (Oximes)
      0 (Pralidoxime Compounds)
      0 (Pyridinium Compounds)
      120103-35-7 (HLo 7)
      19SQ93LM6H (diacetylmonoxime)
      61444-84-6 (N,N'-monomethylenebis(pyridiniumaldoxime))
      7C0697DR9I (Atropine)
      B4XG72QGFM (Sarin)
      EC 3.1.1.7 (Acetylcholinesterase)
      K324J5K4HM (Diacetyl)
      KVI301NA53 (Pyridostigmine Bromide)
      P7MU9UTP52 (pralidoxime)
    • Publication Date:
      Date Created: 20090815 Date Completed: 20100421 Latest Revision: 20211020
    • Publication Date:
      20240829
    • Accession Number:
      10.1007/s12031-009-9259-7
    • Accession Number:
      19680820