OBJECTIVETo explore the inhibitory effects of highly toxic organophosphorus compound and its substitute (methamidophos and acephate) on acetylcholinesterase (AChE) and their toxic mechanisms.

METHODSEllman method was used to measure AChE activity in vitro and vivo.

RESULTSAcephate and methamidophos could directly inhibit AChE activities in human erythrocyte membrane and rat brain synatosomal membrane in dose- and time-dependent manners in vitro, and this effect was irreversible. The IC50 of acephate and methamidophos affecting human erythrocyte membrane and rat synatosomal membrane were approximately 10(-4) mol/L and 10(-5) mol/L respectively and the Ki were 10(2) mol.L-1.min-1 and 10(3) mol.L-1.min-1 respectively. In vivo, after rats being administered with them for 5 d, the inhibitory rate of AChE activities in blood were increased to 68.24% and 54.80% respectively. When rats being administrated with acephate, there was 31.68% of inhibition on the brain stem, but no significant inhibition in other brain region was noticed, while methamidophos had a strong inhibitory effect on the activity of AChE in all brain regions, especially the cerebellum and brain-stem(71.51% and 61.85% respectively).

CONCLUSIONAcephate and methamidophos could directly inhibit the AChE activities in vitro, but the inhibition degree was different. In vivo, both could also inhibit AChE activities in blood. The difference in inhibition on brain regions may be one of the reason of various toxic effect of them.