The protective ratio produced by
HI-6 (with
atropine) against
soman and
tabun poisoning in rats and guinea pigs was determined. The amount of protection afforded by
HI-6 decreased with time following
poisoning, prompting us to examine the effects of repeated doses of
HI-6 (four additional) given over a 5-hr period. In addition, it was determined that
HI-6 produced much better protection in female rats than male rats, which led to a study of the
hormone dependence of this activity. When in addition to the first dose of
HI-6 four additional doses were given over a 5-hr period, the protective ratio, defined as LD50 in treated animals/LD50 in untreated animals, in males against
soman, increased from 4.2 to 7.8, and against
tabun, from 2.5 to 6.6. A single dose of
HI-6 produced a protective ratio in females of 10.5 against
soman and 4.3 against
tabun, whereas multiple doses increased these values to greater than 27 and 22, respectively. A regimen consisting of gonad removal and long-term treatment with a
sex hormone of the opposite gender reversed the sex-related differences in response to the protective effects of
HI-6. In addition a single injection of
HI-6 (plus
atropine), 1 min following either
soman or
tabun, produced good protective ratios in guinea pigs against both
soman (between 4 and 5) and
tabun (5.1); however, there was no apparent
hormone-dependent effect similar to that obtained in rats. The results demonstrate unequivocal protective effects of
HI-6 against
tabun and a very dramatic
hormone-dependent factor in its activity against either
organophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)