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A microdialysis study of glycinamide, glycine and other amino acid neurotransmitters in rat frontal cortex and hippocampus after the administration of milacemide, a glycine pro-drug

  • Mary H. Doheny
  • Shigeru Nagaki
  • Philip N. Patsalos
Original Article

Abstract

Milacemide is a glycinamide derivative which readily enters the brain and is metabolised to glycine. As its mechanism of action as an anticonvulsant drug is unknown we used the technique of microdialysis to study the temporal inter-relationship of glycinamide, glycine and other amino acid neurotransmitters in the extracellular fluid of rat hippocampus and frontal cortex. After milacemide administration (400 or 800 mg/kg i.p.), glycinamide concentrations rose linearly and dose-dependently in both hippocampus and frontal cortex. In contrast, whilst glycine concentrations rose in the hippocampus, glycine was unaffected in the frontal cortex. Concomitant increases in taurine hippocampal concentrations were observed. An increase in serine and a decrease in alanine concentrations was only observed at the highest milacemide dose (800 mg/kg). Other amino acids were unaffected. Thus, while glycinamide appears to be universally distributed throughout the brain, its metabolism to glycine and its effects on brain amino acids appear to be region specific.

Key words

Milacemide Glycine pro-drug Microdialysis Hippocampus Frontal cortex Amino acids 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Mary H. Doheny
    • 1
  • Shigeru Nagaki
    • 1
  • Philip N. Patsalos
    • 1
  1. 1.Pharmacology and Therapeutics Unit, Epilepsy Research Group Department of Clinical NeurologyInstitute of Neurology Queen SquareLondonUK

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