Doheny M H, Nagaki S, Patsalos P N
Department of Clinical Neurology, Institute of Neurology, London, UK.
Naunyn Schmiedebergs Arch Pharmacol. 1996 Jul;354(2):157-63. doi: 10.1007/BF00178715.
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.
米拉美胺是一种甘氨酰胺衍生物，它能迅速进入大脑并代谢为甘氨酸。由于其作为抗惊厥药物的作用机制尚不清楚，我们采用微透析技术研究了大鼠海马体和额叶皮质细胞外液中甘氨酰胺、甘氨酸及其他氨基酸神经递质的时间相互关系。腹腔注射米拉美胺（400或800毫克/千克）后，海马体和额叶皮质中的甘氨酰胺浓度呈线性上升且具有剂量依赖性。相比之下，虽然海马体中的甘氨酸浓度升高，但额叶皮质中的甘氨酸不受影响。同时观察到海马体中牛磺酸浓度增加。仅在最高米拉美胺剂量（800毫克/千克）时观察到丝氨酸增加和丙氨酸浓度降低。其他氨基酸也受到影响。因此，虽然甘氨酰胺似乎在整个大脑中普遍分布，但其代谢为甘氨酸及其对脑氨基酸的影响似乎具有区域特异性。
