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© 1990 Oxford University Press

other

Evaluation of the Efficacy of Two Carbamates, Physostigmine and Pyridostigmine, When Used in Conjunction for Protection against Organophosphate Exposure1,2

RICHARD P. SOLANA3, CHRIS GENNINGS*, WALTER H. CARTER, JR.,*, DANA ANDERSON, WILLARD J. LENNOX, RICHARD A. CARCHMAN* and LARREL W. HARRIS

*Departments of Pharmacology/Toxicology and Biostatistics, Medical College of Virginia Richmond, Virginia 23298 U.S. Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, Maryland 21010–5425

Received February 12, 1990; accepted July 12, 1990

Evaluation of the Efficacy of Two Carbamates, Physostigmine and Pyridostigmine, When Used in Conjunction for Protection against Organophosphate Exposure. SOLANA, R. P., GENNINGS, C., CARTER, W. H., JR., ANDERSON, D., LENNOX, W.J., CARCHMAN, R. A., AND HARRIS, L. W. (1990). Fundam. Appl Toxicol. 15, 814–819. Recent studies have shown that pretreatment with either pyridostigmine (PYR) or physostigmine (PHY) followed by atropine-oxime therapy is very effective in reducing the lethality of nerve agents. The therapeutic efficacy of a PHY and PYR combination pretreatment was evaluated in guinea pigs challenged with two LD50s of soman. Endpoints measured were percentage of acetylcholinesterase inhibition induced by the pretreatment and survival up to 24 hr postchallenge. Response surface methodology was employed to describe the relationship between each endpoint and the pretreatment combination. Although both carbamates contributed to blood acetylcholinesterase inhibition, PHY alone protected as well as the optimal dose of the combination.


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