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 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 affected. 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.
Doheny
M H
MH
Department of Clinical Neurology, Institute of Neurology, London, UK.
Nagaki
S
S
Patsalos
P N
PN
D000081:Acetamides / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000081:Acetamides; D000596:Amino Acids; D000927:Anticonvulsants; D011355:Prodrugs; C039332:milacemide; C018556:glycine amide; D005998:Glycine