Relationship between the neurotoxicities of Soman, Sarin and Tabun, and acetylcholinesterase inhibition.
Acetylcholinesterase (AChE)-induced chewing movements, tremors, convulsions and hind limb abduction at doses of 50-85% LD50 in rats were monitored in order to determine whether the severity of these different signs would correlate with brain AChE levels and the time course of such a relationship. 30 min after subcutaneous (s.c.) injection of Soman, the intensities of toxic signs were significantly correlated with the degree of striatal AChE inhibition. In the case of Sarin, the corresponding r-values were not significant except for tremors. For Tabun-induced chewing, tremor and hind-limb abduction, the r-values were significant. The neurotoxicity was most intense between 15 min to 2 h after treatment, but at 2 or 6 h, the r-values were well below 0.5. The inhibition of brain AChE was maximal by 30 min and was still high at 24 h.
B
B
Hoskins
J C
JC
Fernando
M D
MD
Dulaney
D K
DK
Lim
D D
DD
Liu
H K
HK
Watanabe
I K
IK
Ho
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D008409:Mastication / Q000187:drug effects; D010755:Organophosphates / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012524:Sarin / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced; D012999:Soman / Q000633:toxicity*; D014202:Tremor / Q000139:chemically induced
D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D009943:Organophosphorus Compounds; D012999:Soman; D012524:Sarin; C009374:tabun