부산대학교 도서관

The in vitro inhibitory potencies of several nerve agents and other organophosphorus compounds against acetylcholinesterase (AChE) and neurotoxic esterase (NTE) have been compared. Although the I50s against AChE were about 0.1–1.0 nM for the nerve agents the I50s against NTE for sarin, soman and tabun were two to four orders of magnitude higher and VX had negligible activity. A series of bis[(?-phenyl-n-alkyl]phosphorofluoridates inhibited both enzymes at 1.0–100 nM while ?-phenyl-n-alkyl NN-dimethylphosphoramidofluoridates were active at 0.1–10 µM. From the in vitro data it was predicted that nerve agents would cause delayed neuropathy only at doses greatly exceeding the LD50. In hens protected against acute toxicity by pretreatment with physostigmine, atropine and the oxime P2S, delayed neuropathy associated with high inhibition of NTE was found at 30–60 × LD50 for sarin but not at 38 × LD50 for soman or 82 × LD50 for tabun. At the maximum doses tested of the latter two compounds the inhibition of NTE was 55% and 66% respectively. The minimum neuropathic doses were calculated to be about 100–150 × LD50 for soman and tabun.