Biological responsiveness to cholinesterase inhibition: a test for exploring the developmental maturity of the cholinergic system.

The acute mortality caused by two irreversible inhibitors of cholinesterases [diisopropylfluorophosphate (DFP) and diethoxyphosphorylthiocholine, 217 MI-phospholine iodide] has been investigated on chick embryos at different stages of development. The results demonstrate that the above compounds do not show any acute lethal action when administered before the 9th day of incubation; on the other hand, the administration is regularly followed by death after the 9th day of incubation. The doses are comparable to those causing death in hatched chicks. It has also been observed that no appreciable difference exists in DFP uptake from the yolk before and after the 9th day of incubation and that drug-induced cholinesterase inhibition is of the same order of magnitude at any developmental stage; the compound pyridine-2-aldoxime methanesulfonate (2-PAM) was a good antidote against DFP acute lethality. It seems likely that between the 8th and the 9th day of incubation the target system of organophosphorus inhibitors, that is, the cholinesterase enzymatic system, reaches a new point of maturation.