The primary goal of the modification to this contract is to discover small molecules that attenuate seizure activity precipitated by acute exposure to chemical threat agents defined as: toxic chemical agents that could be used in a terrorist attack against civilians, or those that could be released at toxic levels by accident or natural disaster. These include organophosphorus nerve agents and pesticides and cyanide. The further intent of modifying this contract is to take advantage of the economies of scale that already exist by utilizing a portion of the existing anti-convulsant screening mechanisms contractually already in place. We envision two tracts for newly submitted compounds. In the first, compounds will continue to be submitted to the program being screened under the current ASP anticonvulsant model at the rate of 750 per year. The second tract (the work described herein)will be directed specifically at uncovering potential leads against chemical threats. Several new models specific for these purposes are described below. In addition, relevant models already existing as part of the current ASP capacity will be employed to enhance the determination of pharmacological profiles in both CNS protection and toxicity of candidate compounds. It is expected that another 750 compounds can be evaluated in tract two. The combined capacity will be approximate 1500 compounds per year. Costs associated with the different tracts will be monitored and reported separately by the contractor. It is recognized that a combination of submission types will occur. These include: 1) submission to chemical threat screening for compounds that already have preliminary ASP data otherwise called transferred compounds 2) compounds submitted for dual evaluations (traditional ASP and chemical threats) and 3) compounds submitted solely for the tract two (chemical threat agents) portion. Tracking of expenditures for each type must be maintained and submitted in regular quarterly reports (see general requirement section).
