The prophylactic efficacy of various simulators against intoxication with the organophosphate soman: structure-activity studies.
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 X 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 mumol kg-1; its i.v. LD50 appeared to be higher than 1 mmol kg-1.
van Helden
H P
HP
Benschop
H P
HP
Wolthuis
O L
OL
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects
D012999:Soman