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October 1964

Cortical Alterations Due to Methionine Sulfoximine: Ultrastructure During Seizure Activity

Author Affiliations

Division of Neurosurgery, Department of Neurology and the Beaumont-May Institute of Neurology, Washington University School of Medicine.
Work supported by Program-Project grant NB 04513-01, National Institute of Neurological Diseases and Blindness, and in part by the Allen P. and Josephine B. Green Foundation.

Arch Neurol. 1964;11(4):388-407. doi:10.1001/archneur.1964.00460220050008

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 Bentley2-4 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 monkeys7-9 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