Inhibition of acetylcholinesterase in different parts of the brain of mice by isopropyl methylphosphonofluoridate in vitro and in vivo.

Abstract

AChE activity in four parts of the mouse brain, i.e. in the pons and medulla oblongata, mesencephalon, diencephalon and basal ganglia, was inhibited in vitro by isopropyl methylphosphonofluoridate. The inhibition constants, n (Hill coefficient) and I50 were determined. The values of both constants, n and I50, were the same for all studied parts of the brain (n=1.7 and I50=5.0 × 10−10 M). In experiments in vivo, mice were administered the poison in doses ranging from 1.4 to 28.6 mol×10−7/kg, i.e., 0.02 to 0.40 mg/kg. AChE activity was then measured and the degree of inhibition was correlated with the dose of organophosphate given. AChE in the basal ganglia was the most resistant. The highest degree of inhibition was observed in the ponto-medullar portion. This selective inhibition lends support to a concept of this particular portion of the brain as having special importance in the toxidynamics of poisoning. The comparison of AChE inhibition in vitro and in vivo suggests that only about 1% of an injected dose is involved inhibiting AChE in the brain.