Cholinesterase Inhibition by Parathion in vivo

Abstract

WE have shown¹ that OO-diethyl-O-p-nitrophenyl thiophosphate, an insecticidal compound generally known as parathion or E605, has not, when pure, any measurable in vitro inhibition of rat's brain cholinesterase. Nevertheless, pure parathion is a powerful inhibitor of cholinesterase in vivo, and there is little doubt that its mammalian toxicity is due to this property. When parathion is administered intraperitoneally to male rats (180–220 gm.) the dose necessary to produce a 50 per cent inhibition of brain cholinesterase within 30 min. is about 1.5 mgm./kgm., a figure of the same order as that required for OS-diethyl-O-p-nitrophenyl thiophosphate, the S-ethyl isomer of parathion, which is a highly active in vitro inhibitor¹. With a dose of 3 mgm./kgm. the onset of the typical symptoms of parasympathetic stimulation occurs within 10 min. with both compounds. The cholinesterase activity of rat's blood, which is mainly due to specific enzyme in the red cells, is also unaffected by parathion in vitro; but in vivo it can readily be completely inhibited by injected parathion. There is, however, a slight but significant difference between the action of parathion and its S-ethyl isomer in vivo; when a dose of the former, which produces complete inhibition, is administered intravenously, there is a lag of a few minutes before the inhibition develops, whereas with the same dose of the latter the inhibition reaches completion very rapidly after injection.