The prophylactic efficacy of various simulators against intoxication with the organophosphate soman: structure-activity studies

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Abstract
The effects were investigated of structural variations of the soman simulator pinacolyl dimethylphosphinate on its efficacy to prevent secondary failure of oxime-induced recovery of neuromuscular transmission and death after soman intoxication. The simulators were administered prophylactically to atropinized, HI-6 treated rats, dosed with 6 or 8 × LD50 soman. In these new simulators the pinacolyl moiety was varied, the phosphonyl oxygen atom was replaced by sulphur, or the phosphorous-bound methyl groups were replaced by ethyl or methoxy groups. All these variations appeared to be less active than pinacolyl dimethylphosphinate. Intravenously, the latter compound was very effective at a dose of 12 μmol kg−1; its i.v. LD50 appeared to be higher than 1 mmol kg−1.