Watabe S, Yamaguchi H, Ashida S
Exploratory Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Eur J Pharmacol. 1993 Jul 20;238(2-3):303-9. doi: 10.1016/0014-2999(93)90861-b.
DM-9384 (nefiracetam) (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide), a pyrrolidone derivative (or a cyclic derivative of gamma-aminobutyric acid (GABA)), is a newly developed nootropic (or cognition-enhancing) agent. In the present study, we examined the biochemical effect of DM-9384 on GABAergic neurons in adult rat brains. DM-9384, when administered orally at a daily dose of 10 mg/kg for 7 days, significantly increased GABA turnover and glutamic acid decarboxylase activity in the cortex and hippocampus, and stimulated Na(+)-dependent high-affinity GABA uptake in cortical synaptosomes. In in vitro experiments, the K(+)-evoked release of [14C]GABA from cortical slices was markedly increased by low concentrations (10(-8), 10(-9) M) of DM-9384. The binding of GABAA and benzodiazepine to their receptors in the brain was not affected by DM-9384 (10(-10)-10(-3) M). The results suggest that DM-9384 increases the turnover of components of the GABAergic system by influencing presynaptic sites rather than postsynaptic sites.
DM - 9384（奈非西坦）（N - (2,6 - 二甲基苯基)-2 - (2 - 氧代 - 1 - 吡咯烷基)乙酰胺），一种吡咯烷酮衍生物（或γ - 氨基丁酸（GABA）的环状衍生物），是一种新开发的促智药（或认知增强剂）。在本研究中，我们检测了DM - 9384对成年大鼠脑内GABA能神经元的生化作用。当以每日10 mg/kg的剂量口服给药7天时，DM - 9384显著增加了皮质和海马中的GABA周转率以及谷氨酸脱羧酶活性，并刺激了皮质突触体中依赖钠的高亲和力GABA摄取。在体外实验中，低浓度（10^(-8)，10^(-9) M）的DM - 9384显著增加了皮质切片中由钾离子诱发的[14C]GABA释放。DM - 9384（10^(-10) - 10^(-3) M）对脑内GABAA和苯二氮䓬与其受体的结合没有影响。结果表明，DM - 9384通过影响突触前位点而非突触后位点来增加GABA能系统成分的周转率。
