The bispyridinium
oxime HI-6, 1-((((4-amino-carbonyl)pyridinio)methoxy) methyl)-2-(hydroxyimino)methyl)pyridinium dichloride monohydrate, combined with
atropine is an effective treatment for
soman (
pinacolyl methylphosphonofluoridate)
poisoning but is relatively ineffective against
tabun (ethyl N-dimethyl phosphoroamidocyanidate)
poisoning in mice. This contrasts with those results obtained using the bispyridinium
oxime obidoxime[1,1'-(oxy bis(methylene)) bis(4-(hydroxyimino)methyl) pyridinium dibromide]. The purpose of this study was to investigate the efficacy of the combination of
HI-6 and
obidoxime plus
atropine against
poisoning by
tabun and
soman in mice. The combination of ineffective single doses of
obidoxime (5 or 10 mg/kg) and
HI-6 (25 or 50 mg/kg) improved the treatment of
tabun poisoning over either
oxime alone. Combinations employing higher concentrations of
obidoxime (25 or 50 mg/kg) and
HI-6 (100 or 200 mg/kg) resulted in significant toxicity in the absence of
organophosphate poisoning. Against
soman poisoning the addition of
obidoxime to
HI-6 did not attenuate the efficacy of
HI-6. The half-life of elimination and peak serum concentrations of
HI-6 and
obidoxime were not altered following administration of the combined injection. Reactivation of
tabun-inhibited
acetylcholinesterase was found consistently in the diaphragm but not in the brain. Using response surface methods it was possible to estimate the optimal
therapy against
soman and
tabun poisoning (74.5 mg/kg
HI-6 + 31.9 mg
obidoxime against 1052 microns/kg
obidoxime against 390 microns/kg challenge of
soman).(ABSTRACT TRUNCATED AT 250 WORDS)