Cortical Alterations Due to Methionine Sulfoximine

Abstract

Introduction In 1946, Mellanby¹ showed 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 Bentley^2-4 and by Misani and Reiner,^5,6 proved 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 monkeys^7-9 and neither of these changes in epileptic patients.¹⁰ Seizures have been prevented by giving large protective doses of methionine before commencing an experiment.¹¹ The observations based on agenized flour administration have been shown to be less reliable since a calculated maximum