HUPERZINE A AS A PRETREATMENT CANDIDATE DRUG AGAINST NERVE AGENT TOXICITY

Huperzine A (HUP) is a naturally-occurring, potent, reversible inhibit or of acetylcholinesterase (AChE) that crosses the blood-brain barrier . To examine its ability to protect against nerve agent poisoning, HUP was administered i.p. to mice, and the s.c. LD(50) of soman was deter mined at various time intervals after pretreatment. Results were compa red to those obtained for animals treated with physostigmine. A protec tive ratio of approximately 2 was maintained for at least 6 hr after a single injection of HUP, without the need for any post-challenge drug therapy. By contrast, pretreatment with physostigmine increased the L D(50) of soman by 1.4- to 1.5-fold for only up to 90 min. The long-las ting antidotal efficacy displayed by HUP correlated with the time cour se of the blood-AChE inhibition. The results suggest that the protecti on of animals by HUP from soman poisoning was achieved by temporarily sequestering the active site region of the physiologically important A ChE.