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*(L)-METHIONINE
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*Seizures
Journal of Pharmacology And Experimental Therapeutics, Vol. 164, Issue 1, 212-222, 1968
Copyright © 1968 by American Society for Pharmacology and Experimental Therapeutics

METHIONINE SULFOXIMINE SEIZURES. VIII. THE DISSOCIATION OF THE CONVULSANT AND GLUTAMINE SYNTHETASE INHIBITORY EFFECTS

OTTO Z. SELLINGER 1, JULIO M. AZCURRA 1, and WAYNE G. OHLSSON 1

1 Mental Health Research Institute, University of Michigan Medical Center, Ann Arbor, Michigan

A number of derivatives and analogs of L-methionine were found to be effective antagonists of the convulsant L-methionine-DL-sulfoximine (MSO) in the rat. When given together with MSO, D-methionine also protected, but agr-methyl-dl-methionine was ineffective. The effectiveness of the antagonists could be modulated by the injection route, the intraperitoneal route proving more effective than the intraventricular one. The inhibition by MSO of cerebral glutamine synthetase transferase (GT) was examined concurrently in homogenates of the cortex, cerebellum, hypothalamus and thalamus from as early as 30 min to as late as 12 days post-MSO. Inhibition of GT was found to be a direct consequence of the presence of MSO, but was not directly seizure-related. Thus, animals could be protected against seizures in the face of a virtual block of GT activity, and, conversely, seizures could be elicited in the face of relatively elevated enzyme levels. GT inhibition by MSO and protection by l-methionine were also examined in six subcellular fractions of the cortex. Upon subfractionation of the microsomal fraction into "rough" and "smooth" membranes, a preferential protection of the GT component associated with smooth membranes was revealed.

Submitted on December 18, 1967
Accepted on July 8, 1968




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Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics.