Anticonvulsant drug action and regional neurotransmitter amino acid changes.
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 (beta-methylene-aspartate). Beta-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 mumoles (icv; clonic phase). Forebrain and cerebellar aspartate, glutamate and GABA levels are reduced by 15-30% following the administration of beta-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 (100 mg/kg; 3 hours) there were significant increases in rat brain glycine levels in the cerebellum (+137%), cortex (+45%) and hippocampus (+59%).
D000081:Acetamides / Q000627:therapeutic use; D000161:Acoustic Stimulation; D000596:Amino Acids / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000502:physiology*; D012640:Seizures / Q000097:blood / Q000188:drug therapy
D000081:Acetamides; D000596:Amino Acids; D000927:Anticonvulsants; D018377:Neurotransmitter Agents; C039332:milacemide; D001224:Aspartic Acid; C036683:beta-methyleneaspartate