Evaluation of a two-drug combination pretreatment against organophosphorus exposure

Richard P. Solana, Larrel W. Harris, Walter H. Carter, Brian G. Talbot, Richard A. Carchman, Chris Gennings

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


A pretreatment combination of physostigmine and azaprophen (6-methyl-6-azabicyclo[3.2.1]octan-3-ol-2,2-diphenylpropionate), a novel cholinolytic, was evaluated for its ability to minimize soman-induced incapacitation and lethality in guinea pigs. Thes was accomplished by using response surface methodology to model and analyze the combination, varying physostigmine from 0 to 194 μg/kg, azaprophen from 0 to 5 mg/kg, and soman from 30 to 150 μg/kg. One hundred percent survival was achieved against 5 LD50 of soman using as little as 100 μg/kg of physostigmine in the presence of 5 mg/kg azaprophen. Both survival and soman-induced incapacitation were similarly affected by this pretreatment combination. For both endpoints, greater efficacy was achieved with the combination than could be achieved with either component alone (therapeutic synergism). This suggests that such a pretreatment combination may prove very efficacious against soman-induced lethality and incapacitation in higher species.

Original languageEnglish
Pages (from-to)421-429
Number of pages9
JournalToxicology and Applied Pharmacology
Issue number3
StatePublished - 1 Mar 1990
Externally publishedYes


Dive into the research topics of 'Evaluation of a two-drug combination pretreatment against organophosphorus exposure'. Together they form a unique fingerprint.

Cite this