Anticonvulsant drug action and regional neurotransmitter amino acid changes

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Abstract
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%).