1990Toxicological SciencesRequires access

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

Richard P. Solana, Chris Gennings, Walter H. Carter, Dana R. Anderson, W.J. Lennox, Richard A. Carchman, Larrel W. Harris

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Abstract

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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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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Available abstract

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.

Key concepts: Pyridostigmine, Physostigmine, Soman, Organophosphate, Cholinesterase, Acetylcholinesterase, Nerve agent, Pyridostigmine Bromide

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