A comparison of the efficacy of acetylcholinesterase reactivators against cyclohexyl methylphosphonofluoridate (GF agent) by in vitro and in vivo methods

The purpose of this study was to compare the therapeutic efficacy of a new acetylcholinesterase reactivator, designated BI-6 (1-(2-hydroxyiminomethylp yridinium)-4-(4-carbamoylpyridinium)-2-butene dibromide), with presently us ed oximes (pralidoxime, obidoxime, methoxime) and H-oximes (HI-6, HLo-7) by in vitro and in vivo methods. In vitro, methoxime seems to be the most eff icacious reactivator of GF agent-inhibited acetylcholinesterase because the phosphonylation of acetylcholinesterase by GF agent markedly increases its affinity for the enzyme. The oxime BI-6 is more efficacious than other pre sently used oximes (pralidoxime, obidoxime) but its reactivating efficacy d oes not reach the efficacy of H-oximes tested. On the other hand, obidoxime and pralidoxime appear to be very poor reactivators of GF agent-inhibited acetylcholinesterase because the phosphonylation of acetylcholinesterase by GF agent markedly decreases their affinity to the enzyme. In vivo, H oxime s (HI-6, HLo-7) are the most efficacious antidotes for the treatment of acu te poisoning with GF agent in rats while the presently used oximes such as pralidoxime and obidoxime are practically ineffective. BI-6 and methoxime a re more efficacious than pralidoxime and obidoxime, nevertheless their ther apeutic efficacy does not reach the efficacy of H oximes. Our results show that the ability of oximes to reactivate GF agent-inhibited acetylcholinest erase in vitro usually corresponds to their therapeutic effects against GF agent in vivo.