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© 1990 Oxford University Press

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Assessing the Efficacy of Azaprophen and Physostigmine as a Pretreatment for Soman-Induced Incapacitation in Guinea Pigs by Response-Surface Modeling1

CHRIS GENNINGS*, WALTER H. CARTER, JR.*, LARREL W. HARRIS{dagger}, RICHARD A. CARCHMAN*, ELEANOR D. CAMPBELL*, RUSSELL M. BOYLE*, BRIAN G. TALBOT{dagger} and RICHARD P. SOLANA{dagger}

*Medical College of Virginia/Virginia Commonwealth University Richmond, Virginia {dagger}U.S. Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, Maryland

Received January 17, 1989; accepted August 25, 1989

Assessing the Efficacy of Azaprophen and Physostigmine as a Pretreatment for Soman-lnduced Incapacitation in Guinea Pigs by Response-Surface Modeling. GENNINGS, C, CARTER, W. H., JR., HARRIS, L. W., CARCHMAN, R. A., CAMPBELL, E. D., BOYLE, R. M., TALBOT, B. G., AND SOLANA, R. P. (1990). Fundam. Appl. Toxicol. 14, 235–242. Physostigmine (PHY) has the advantage over pyridostigmine of minimizing OP-induced incapacitation because it penetrates into the CNS. However, physostigmine is behaviorally toxic at relatively low concentrations. It is anticipated that this could be offset by a cholinolytic to prevent behavioral deficit due to the carbamate pretreatment alone. The therapeutic efficacy of physostigmine/azaprophen pretreatment therapy was evaluated in soman-challenged guinea pigs. Response surface methodology was employed to describe the relationship of the pretreatment combination with duration of incapacitation. The significance of the combination relative to PHY alone was evaluated in addition to dose combinations that yield optimal time to recovery. Analysis of the fitted response surface indicated that combination pretreatment with these compounds significantly reduces the time to recovery after soman challenge versus pretreatment with PHY alone.


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