Comparing the Efficacy of Physostigmine Pretreatment in Combination with Scopolamine Versus Artane against Soman Challenge

摘要

Physostigmine (PHY) is currently being evaluated as a potential pretreatment against nerve agent challenge. Because it penetrates into the central nervous system (CNS), it has the advantage over pyridostigmine of minimizing post-challenge incapacitation, presumably by protecting CNS acetylcholinesterase (AChE). Nonetheless, PHY is behaviorally toxic at relatively low concentrations. The identification of a combination pretreatment which minimizes the dosage of PHY is expected to minimize the PHY side effects. This could provide the soldier with a pretreatment that not only is without behavioral decrement by itself, but also has an advantage over pyridostigmine of minimizing incapacitation due to agent exposure. In a combination exposure the potential interactions between the components can be very complex. It is difficult to discern how much each compound would contribute to an observed effect. In previous work, artane (ART) and scopolamine (SCP), as adjuncts to PHY pretreatment, have been shown to be effective against lethality and nonlethal effects of soman (GD) challenge. In this study Response Surface Methodology (RSM) was employed to evaluate the efficacy of PHY combined with either SCP or ART as a pretreatment for soman-induced responses. Three endpoints involving survival and behavioral evaluations are considered for comparison. The goal was to determine if either cholinolytic is more effective as a pretreatment for soman intoxication when given in combination with PHY. (kt)