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

Milacemide is a glycinamide derivative which readily enters the brain and is metabolised to glycine. As its mechanism of action as an antico nvulsant drug is unknown we used the technique of microdialysis to stu dy the temporal inter-relationship of glycinamide, glycine and other a mino acid neurotransmitters in the extracellular fluid of rat hippocam pus and frontal cortex. After milacemide administration (400 or 800 mg /kg i.p.), glycinamide concentrations rose linearly and dose-dependent ly 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 concentr ations were observed. An increase in serine and a decrease in alanine concentrations was only observed at the highest milacemide dose (800 m g/kg). Other amino acids were unaffected. Thus, while glycinamide appe ars to be universally distributed throughout the brain, its metabolism to glycine and its effects on brain amino acids appear to be region s pecific.