Cortical Alterations Due to Methionine Sulfoximine

Abstract

Introduction In 1946, Mellanby1showed that the nitrogen trichloride treatment used for bleaching (agenizing) flour acted on proteins to produce a toxic product that caused running fits (so-called canine hysteria) in dogs. This toxic substance, isolated and later synthesized by Bentley2-4and by Misani and Reiner,5,6proved to be methionine sulfoximine,*an analogue and competitive antimetabolite of methionine. It has been shown to produce seizures in a number of species. Earlier workers, using agenized flour, have shown EEG changes but not seizures in monkeys7-9and neither of these changes in epileptic patients.10Seizures have been prevented by giving large protective doses of methionine before commencing an experiment.11The observations based on agenized flour administration have been shown to be less reliable since a calculated maximum