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Decreased GABA and glutamate concentration in rat brain after treatment with 6-aminonicotinamide

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Summary

The 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:

  1. a)

    The changes in the concentration of neurotansmitters as GABA and glutamate could be resonsible for some neurological symptoms produced by 6-AN.

  2. b)

    As 6-AN seems to affect the GABA-shunt it represents a model substance for studying this pathway in the nervous system.

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Bielicki, L., Krieglstein, J. Decreased GABA and glutamate concentration in rat brain after treatment with 6-aminonicotinamide. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 157–160 (1976). https://doi.org/10.1007/BF00507848

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  • DOI: https://doi.org/10.1007/BF00507848

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