Medical Research and Evaluation Facility and Studies Supporting the MedicalChemical Defense Program. Screening of Candidate Pretreatment and Therapeutic Compounds in In Vivo Models

摘要

Therapeutic compounds under consideration to protect soldiers exposed to Soman(GD), Tabun (GA), and sodium cyanide (NaCN) were evaluated in in vivo mouse models. Compounds were provided by the Basic Assessment Branch, Drug Assessment Division, U.S. Army Medical Research Institute of Chemical Defense (MRICD), through the Division of Experimental Therapeutics, Walter Reed Army Institute of Research. Candidate compounds were evaluated for solubility, range-finding and definitive LD5O, and efficacy in countering the effects of exposure to nerve agents or NaCN. To determine the LD5O compounds were tested at their limit of solubility, if no lethality was observed, then a more definitive study was not conducted. If treated animals died, then further range-finding studies were conducted to determine the LD5O. Test doses used in efficacy studies were based either on limits of solubility or LD5O values. A test compound was deemed effective if at any of three concentrations tested, it was statistically more efficacious in prevent lethality than the compound solvent solution.