Dealkylation and Loss of Capacity for Reactivation of Cholinesterase Inhibited by Sarin

Abstract

Inhibition of rat brain acetylcholinesterase by ³² P-sarin in vivo results initially in ³² P-isopropylmethylphosphonylated enzyme. The percentage of inhibited enzyme that could not be reactivated by pyridinium aldoxime methochloride (aged enzyme) approximated the amount of radioactivity identified as ³² P-methylphosphonate. The ³² P-isopropyl methylphosphonate not released from the inhibited enzyme by the oxime accounted for 51 ± 10 percent (standard deviation) of the radioactivity fixed to brain tissue. It showed no correlation with aging and was probably bound to sites other than acetylcholinesterase.