EFFICACY OF TACRINE AS A NERVE AGENT PRETREATMENT

Tacrine (THA) was evaluated in vitro and in vivo as a pretreatment for nerve agent intoxication. In vitro experiments showed that the primar y effect of THA was direct inhibition of purified fetal bovine serum a cetylcholinesterase (AChE) with a slight effect on slowing the aging r ate of nerve agent-inhibited AChE. THA produced significant behavioral effects at doses above 1.7 mg/kg, i.m., in the mouse and 3.4 mg/kg, i .m., in the guinea pig. At the no observable effect level (NOEL) for m ice (1.7 mg/kg), THA was effective (P less than or equal to 0.05) in r educing tabun- and soman-, but not sarin-induced lethality in mice. Ex periments in the guinea pig showed that at the NOEL (3.4 mg/kg, i.m.) THA was not effective in decreasing lethality due to soman exposure. S ince there was significant overlap between pharmacologically effective doses of THA and those which produce behavioral toxicity, THA was not considered a suitable pretreatment for nerve agent intoxication.