TY - JOUR
T1 - Evaluation of a two-drug combination pretreatment against organophosphorus exposure
AU - Solana, Richard P.
AU - Harris, Larrel W.
AU - Carter, Walter H.
AU - Talbot, Brian G.
AU - Carchman, Richard A.
AU - Gennings, Chris
N1 - Funding Information:
The authors are sincerely grateful for the talented technical support provided by Mrs. Campbell. This research was funded in part by U.S. Army Medical Research and Development Command Contract DAMD 17-86-C-6262.
PY - 1990/3/1
Y1 - 1990/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0025255561&partnerID=8YFLogxK
U2 - 10.1016/0041-008X(90)90038-V
DO - 10.1016/0041-008X(90)90038-V
M3 - Article
C2 - 2315913
AN - SCOPUS:0025255561
SN - 0041-008X
VL - 102
SP - 421
EP - 429
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -