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Anticonvulsant drug action and regional neurotransmitter amino acid changes

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Summary

The role played by the inhibitory transmitters, GABA, glycine and taurine, and by excitatory (aspartate/glutamate) antagonists in mediating anticonvulsant action will be documented. This study provides examples of one anticonvulsant compound that affects glycine metabolism (milacemide), and another that affects aspartate metabolism (Β-methylene-aspartate). Β-Methylene-aspartate, a selective inhibitor of glutamate-aspartate transaminase activity, protects against sound-induced seizures in audiogenic DBA/2 mice, with an ED50 value of 1.9 Μmoles (icv; clonic phase). Forebrain and cerebellar aspartate, glutamate and GABA levels are reduced by 15–30% following the administration of Β-methylene-aspartate.

Milacemide, a glycinamide derivative with experimental and clinical anticonvulsant activity, is ineffective against sound-induced seizures in DBA/2 mice. Following the ip administration of milacemide (100mg/kg; 3 hours) there were significant increases in rat brain glycine levels in the cerebellum (+ 137%), cortex (+ 45%) and hippocampus (+ 59%).

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  1. A. G. Chapman

    Present address: Department of Neurology, Institute of Psychiatry, London, England

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  1. Department of Neurology, Institute of Psychiatry, London, England

    G. P. Hart

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  1. A. G. Chapman
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  2. G. P. Hart
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Chapman, A.G., Hart, G.P. Anticonvulsant drug action and regional neurotransmitter amino acid changes. J. Neural Transmission 72, 201–212 (1988). https://doi.org/10.1007/BF01243420

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