Ederey_1966_Toxicol.Appl.Pharmacol_9_341

The passage of 2-hydroxyiminomethyl-N-methylpyridinium methanesulfonate (P2S) to the perfused cerebral spaces of pregnant does and to their fetuses has been studied. The oxime did not penetrate into the fetus after intravenous injection of 30 mg/kg though it did after 60 mg/kg or continuous slow infusion of 2.5 mg/kg/min during 45 minutes. In all cases P2S was found in the perfusate of cerebral spaces. In animals intoxicated with tetraethyl pyrophosphate, the maternal blood cholinesterase was rapidly reactivated after injection of 30 mg/kg of P2S, but both brain and blood cholinesterase activity of the fetuses stayed reduced. Administration of 60 mg/kg reactivated the enzyme also in fetuses. It is suggested that in cases of organophosphate poisoning in pregnant females, high doses of P2S should be administered in order to reach the fetus. Continuous slow infusion of the oxime appears to be the method of choice, as it also maintains a satisfactory constant plasma level.