Behavioral and convulsive phenomena induced in the cat by methionine sulfoximine

Proler, Meyer L.; Kellaway, Peter

doi:10.1212/wnl.15.10.931

Cited by 6 publications

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“…Given the potential use of MSO in humans it is important to understand why some mammals are more sensitive to the effect of this compound than others (Pollock 1949, Proler and Kellaway 1965, Rowe and Meister 1970, Griffith and Meister 1978). Dogs are especially sensitive to MSO (Gershoff and Elvehjem 1951) and also produce two forms of glutamine synthetase distinguished by size (Shin and Park 2004).…”

Section: Discussionmentioning

confidence: 99%

“…One objection to the use of MSO in human is the fact at relatively high concentrations it can cause seizures in a variety of experimental animals (Mellanby 1946, Pollock 1949, Gershoff and Elvehjem 1951, Proler and Kellaway 1965, Boissonnet et al 2012, Boissonnet et al 2013, Sun et al 2013). It was the occurrence of these seizures that led to the discovery of MSO.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine—relevance to the treatment of neurological diseases

Jeitner

Cooper

2013

Metab Brain Dis

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At high concentrations, the glutamine synthetase inhibitor L-methionine-S,R-sulfoximine is a convulsant, especially in dogs. Nevertheless, sub-convulsive doses of MSO are neuroprotective in rodent models of hyperammonemia, acute liver disease, and amyotrophic lateral sclerosis and suggest MSO may be clinically useful. Previous work has also shown that much lower doses of MSO are required to produce convulsions in dogs than in primates. Evidence from the mid-20th century suggests that humans are also less sensitive. In the present work, the inhibition of recombinant human glutamine synthetase with MSO is shown to be biphasic – an initial reversible competitive inhibition (Ki 1.19 mM) is followed by rapid irreversible inactivation. This Ki value for the human enzyme accounts, in part, for relative insensitivity of primates to MSO and suggests that this inhibitor could be used to safely inhibit glutamine synthetase activity in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine—relevance to the treatment of neurological diseases

Jeitner

Cooper

2013

Metab Brain Dis

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Mechanism of Inhibition of Glutamine Synthetase by Methionine Sulphoximine

Meister

Ronzio

Rowe

et al. 1971

A Symposium on Mechanisms of Toxicity

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Glutamine Synthetase: Role in Neurological Disorders

Jayakumar

Norenberg

2016

Advances in Neurobiology

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Glutamine synthetase (GS) is an ATP-dependent enzyme found in most species that synthesizes glutamine from glutamate and ammonia. In brain, GS is exclusively located in astrocytes where it serves to maintain the glutamate-glutamine cycle, as well as nitrogen metabolism. Changes in the activity of GS, as well as its gene expression, along with excitotoxicity, have been identified in a number of neurological conditions. The literature describing alterations in the activation and gene expression of GS, as well as its involvement in different neurological disorders, however, is incomplete. This review summarizes changes in GS gene expression/activity and its potential contribution to the pathogenesis of several neurological disorders, including hepatic encephalopathy, ischemia, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, traumatic brain injury, Parkinson's disease, and astroglial neoplasms. This review also explores the possibility of targeting GS in the therapy of these conditions.

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Behavioral and convulsive phenomena induced in the cat by methionine sulfoximine

Cited by 6 publications

References 0 publications

Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine—relevance to the treatment of neurological diseases

Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine—relevance to the treatment of neurological diseases

Mechanism of Inhibition of Glutamine Synthetase by Methionine Sulphoximine

Glutamine Synthetase: Role in Neurological Disorders

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