Assessing the efficacy of azaprophen and physostigmine as a pretreatment for soman-induced incapacitation in guinea pigs by response-surface modeling.
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.
Gennings
C
C
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
Carter
W H
WH
Harris
L W
LW
Carchman
R A
RA
Campbell
E D
ED
Boyle
R M
RM
Talbot
B G
BG
Solana
R P
RP
D000818:Animals; D016001:Confidence Intervals; D004359:Drug Therapy, Combination; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008954:Models, Biological; D010276:Parasympatholytics / Q000627:therapeutic use*; D010666:Phenylpropionates / Q000627:therapeutic use*; D010830:Physostigmine / Q000627:therapeutic use*; D012999:Soman / Q000037:antagonists & inhibitors*; D014326:Tropanes / Q000627:therapeutic use*
D010276:Parasympatholytics; D010666:Phenylpropionates; D014326:Tropanes; C052339:azaprophen; D012999:Soman; D010830:Physostigmine