It has been shown that
HI-6 was the most potent
oxime so far known in
poisoning by
sarin,
VX , and
soman, but its protective effect in
tabun poisoning, allegedly due to poor reactivation of inhibited ChE, was much less pronounced. We have found that the
thiocholine-like analog of
tabun , O-ethyl, N-N- dimethyamino -S-(2-diethylaminoethyl)- thiophosphatemethylsul fomethylate (Ta-S-N+), was very useful in resolving this problem and established the relationship between reactivating and protective effects of
PAM-2 Cl,
HI-6, and
HGG-12 in rats.
PAM-2 Cl (protective ratio (PR) = 22.1) and
HI-6 (PR = 24.8), combined with
atropine, were very effective against Ta-S-N+
poisoning and reactivating inhibited RBC AChE in vitro and rat blood ChE in vivo. The inefficiency of
PAM-2 Cl (PR = 1.6) and
HI-6 (PR = 2) in
tabun poisoning was due to their inadequacy to reactive
tabun -inhibited
ChEs . The protective effects of
HGG-12 in
tabun (PR = 2.8) and Ta-S-N+
poisoning (PR = 2.6) were low, and in the absence of any reactivation of inhibited
ChEs , have been attributed to its direct pharmacological effects, which were much more potent in the comparison with
PAM-2 Cl or
HI-6. It is concluded that the reactivation of inhibited ChE is of decisive importance in the efficient protection in
poisoning by
tabun and other known chemical warfare
nerve agents, whereas their direct pharmacological effects are of limited value, allowing survival of animals only against a few LD50s .