Accession Number : ADA539650


Title :   In Vivo Reactivation by Oximes of Inhibited Blood, Brain and Peripheral Tissue Cholinesterase Activity Following Exposure to Nerve Agents in Guinea Pigs


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD PHARMACOLOGY BRANCH


Personal Author(s) : Shih, Tsung-Ming ; Skovira, Jacob W ; O'Donnell, John C ; McDonough, John H


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a539650.pdf


Report Date : Jan 2010


Pagination or Media Count : 9


Abstract : This study compared the ability of nine oximes (HI-6, HL 7, MMB-4, TMB-4, carboxime, ICD585, ICD692, ICD3805, and 2-PAM) to reactivate in vivo cholinesterase (ChE) in blood, brain, and peripheral tissues in guinea pigs intoxicated by one of four organophosphorus nerve agents. Two bis-pyridinium compounds without an oxime group, SAD128 and ICD4157, served as non-oxime controls. Animals were injected subcutaneously with 1.0 LD50 of the nerve agents sarin, cyclosarin, VR or VX and treated intramuscularly 5 min later with one of these oximes. Toxic signs and lethality were monitored; tissue ChE activities were determined at 60 min after nerve agent. Some animals exposed to sarin or cyclosarin, with or without non-oxime treatment, died within 60 min; however, no animal treated with an oxime died. For VR or VX, all animals survived the 60 min after exposure, with or without non-oxime or oxime therapy. The four nerve agents caused differential degrees of inhibition in blood, brain regions and peripheral tissues. The tested oximes exhibited differential potency in reactivating nerve agent-inhibited ChE in various peripheral tissues, but did not affect ChE activity in the brain regions. There was no direct relation between blood and peripheral tissues in the reactivating efficacy of oxime treatments. ChE inhibited by sarin was the most susceptible to oxime reactivation while cyclosarin the least susceptible. There was no difference in the ChE reactivating potency between the dimethanesulfonate and dichloride salts of HI-6. MMB-4 significantly reactivated the ChE inhibited by these four nerve agents in blood and all three peripheral tissues of the guinea pig, and among all the oximes tested it was the most effective in vivo ChE reactivator against all four nerve agents.


Descriptors :   *CHOLINESTERASE , *NERVE AGENTS , *OXIMES , TABLES(DATA) , LETHALITY , ACETYLCHOLINESTERASE , HEART , BLOOD , CHEMICAL WARFARE AGENTS , ORGANIC PHOSPHORUS COMPOUNDS , GUINEA PIGS , ANALYSIS OF VARIANCE , BRAIN , REPRINTS , TISSUES(BIOLOGY)


Subject Categories : Biochemistry
      Medicine and Medical Research
      Toxicology
      Pharmacology
      Organic Chemistry
      Chemical, Biological and Radiological Warfare


Distribution Statement : APPROVED FOR PUBLIC RELEASE