L. Bielicki, J. Krieglstein
Aug 1, 1976
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Journal
Naunyn-Schmiedeberg's Archives of Pharmacology
Abstract
SummaryThe effect of 6-aminonicotinamide (6-AN) on putative amino acid neurotransmitters, namely glutamate, GABA and aspartate was studied on brains of rats treated with this antimetabolite (35 mg/kg i.p.).After 6-AN application the following substrates and metabolites were determined: phosphocreatine, ATP, ADP, AMP, glucose, glucose 6-phosphate, fructose 6-phosphate, pyruvate, lactate, α-ketoglutarate, glutamate, GABA, aspartate, ammonia, and 6-phosphogluconate.The alterations in the cerebral energy metabolism were found as reported in the literature (increased levels of glucose, glucose 6-phosphate, decreased levels of lactate and pyruvate) and could be interpreted as the result of a reduced glycolytic flux rate.After a prolonged period of 6-AN pretreatment (16–30 h) the GABA and glutamate concentrations were significantly reduced, whereas the level of aspartate remained unchanged.From the results presented the two following conclusions may be drawn:a)The changes in the concentration of neurotansmitters as GABA and glutamate could be resonsible for some neurological symptoms produced by 6-AN.b)As 6-AN seems to affect the GABA-shunt it represents a model substance for studying this pathway in the nervous system.