Inhibition of acetylcholinesterase in different parts of the rat brain by isopropyl methyl-phosphonofluoridate; in vitro and in vivo experiments

Abstract

Inhibition of AChE in the cerebellum, pons, frontal cortex and basal ganglia of the rat brain by isopropyl methylphosphonofluoridate in vitro was studied and constants characterizing this inhibition (I 50 and bimolecular rate constant, k a were determined. They were practically identical for all parts of the brain studied. In experiments in vivo, the dependence of AChE inhibition on the dose of organophosphate, and the time course of AChE inhibition following dose of 0.25 mg/kg i.m. were studied. The dose required for 50 per cent inhibition of AChE (I 50 dose) was the highest for the basal ganglia and the lowest for the frontal cortex and the cerebellum. The rate of AChE inhibition in vivo was most rapid in the frontal cortex and slowest in the basal ganglia. A correlation between AChE activity in different parts of the brain and I 50 dose of these parts was demonstrated. The differences in inhibition produced in the various areas of the brain are probably caused by different AChE concentration in these structures.