Methionine sulfoximine, toxicity

More recently Braganca, Faulkner, and Quastel (B15) showed that this inhibition of acetylcholine synthesis in brain slices by ammonia is consistent only in the diminution of bound acetylcholine. They further showed that the addition of inhibitors of glutamine synthesis, such as methionine sulfoxide, ethionine sulfoxide, and methionine sulfoximine (the toxic product, causing convulsions, formed in flour chemically aged with nitrogen trichloride) would partially reverse the ammonium inhibition. These observations were confirmed and extended to a wide variety of ATP-requiring reactions by Weil-Malherbe. In support of this suggestion was the observation that ammonia is taken up by the brain in hepatic coma (B8). The observations are valid and have been confirmed, but the interpretation of the data and the hypothesis are questionable. A quantitative basis for the evaluation of this mechanism can... 

Warren, K.S., and S.Schenker. 1964. Effect of an inhibitor of glutamine synthesis (methionine sulfoximine) on ammonia toxicity and metabolism. J. Lab. Clin. Med. 64(3) 442-449. 

Other substances to which people have been exposed have been shown to alter the toxic effects of ammonia. Methionine sulfoximine, administered by intraperitoneal injection, suppressed the tonic convulsions produced by intravenous injection of ammonium chloride in mice (Hindfelt and Plum 1975 Warren and Schenker 1964). Intraperitoneal injection of alpha-methylglutamic acid also exerts a protective effect against hyperammonemia in rats (Lamar 1970). Nicotinohydroxamic acid and neomycin administered orally reduce blood ammonia levels and increase excretion of urea in treated rats (Haiada et al. 1985). Ethanol exerted a protective effect on acute ammonia intoxication in mice (O Connor et al. 

Jeanodda, V. L. R., J. Valisolalao, E. E. Creppy, and G. Dir-heimer. Identification of the toxic principle of Cnestis glabra as methionine sulfoximine. Phytochemistry, 24, 854-855 (1985). 

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