Many research articles have discussed the merits of particular reactivator compounds against specific CWNAs, and several review articles have described the history and protective ratios of Dinaciclib medical countermeasures to OP intoxication (Dawson, 1994, Stojiljković and Jokanović, 2006, Worek et al., 2007 and Antonijevic and Stojiljkovic, 2007). In the following discussion, we review each of the oximes tested in the present study within the context of those historical data. It is important to note that since these historical data have been obtained under vastly different

experimental conditions, e.g., different animal species, doses, timing and routes of administration of the oxime, adjuvants, or challenge materials, the results may not be directly comparable. It is the result of this variability in BGJ398 procedures that necessitated the evaluation of promising oximes within a single study in a standardized and

comparable manner. 2-PAM Cl, first synthesized in 1955 (Childs et al., 1955), is a monopyridinium oxime with the aldoximide in the 2-position. In clinical settings, the use of 2-PAM Cl is contraindicated (Wille et al., 2013) or at least controversial (Rosman et al., 2009) against some pesticide intoxication. In the present study, 2-PAM Cl offered significant survival protection against LD85 challenges of GB, VX, and the pesticide oxons; however significant AChE reactivation was observed only for GB and VX. These data are consistent with the less than optimal utility of unless 2-PAM Cl against GA, GD, and GF observed in this study, and underscore the need for a second generation reactivator for use in the U.S. In vitro reactivation studies using human AChE indicated that 2-PAM Cl was generally the least effective against GA, GB, GF, and VX relative to HLö-7, HI-6, MMB4, and obidoxime (Worek et al., 2007) when compared to the other oximes. A similar study by Cadieux

et al. (2010) also indicated less than optimal in vitro reactivation against GA, GB, GF, VX, and Russian VX (VR) relative to HI-6 and MMB4. In the present study, MMB4 DMS offered significant protection in terms of survivability against all of the OPs at both the equimolar and TI dose levels except GD, likely due to rapid “aging” (irreversible dealkylation of an alkoxy chain on the phosphorus atom) of the GD/AChE conjugate (Vale, 2009). In terms of reactivation of blood AChE and BChE 24-hour post-challenge, MMB4 DMS was superior to the other seven oximes tested. Similar to MMB4 DMS, HLö-7 DMS (at 146 μmol/kg given at 1 min after challenge) was significantly effective against every OP challenge except GD as well. These results concur with the literature in that HLö-7 DMS is a very good candidate for treatment of most OPs (Eyer et al., 1992).