In Vivo Evaluation of the Protective Efficacy of RS194B as a Centrally Acting Reactivator of Nerve Agent-Inhibited Acetylcholinesterase
Technical Report,01 Aug 2016,31 Dec 2018
US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground United States
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RS194B is an oxime that was developed by a group at the University of California at San Diego and is purported to penetrate the central nervous system CNS and reactivate brain acetylcholinesterase AChE inhibited by nerve agents. The first study evaluated the ability of RS194B to reactivate nerve agent-inhibited human or mouse AChE enzyme in vitro. In the second study, RS194B was administered to mice 15 min after they had been challenged with a toxic dose 1xLD50 of the nerve agent sarin GB, VX or cyclosarin GF, and AChE activity was determined using a modified Ellman method. In the third study, mice were challenged with 5xLD50 of GB or VX or 3.5xLD50 of GF and then treated 1 min later with atropine sulfate, midazolam and either RS194B or 2-PAM. Survival at 24 hr was measured. In summary, RS194B produced occasional AChE reactivation in some brain structures inhibited by GB or VX, but not GF, but it did consistently produce reactivation in peripheral tissues and blood. RS194B was no more effective than 2-PAM in providing protection against a 5xLD50 challenge of GB or VX and provided no protection against a 3.5xLD50 GF challenge. RS194B appeared to provide minimal to modest reactivation of brain AChE at best and was no more effective than 2-PAM in protecting against the lethal effects of these nerve agents.
- Chemical, Biological and Radiological Warfare