Mochizuki D, Sugiyama S, Shinoda Y
Exploratory Research Laboratories, Toyo Jozo Co., Ltd., Shizuoka, Japan.
Nihon Yakurigaku Zasshi. 1992 Jan;99(1):27-35. doi: 10.1254/fpj.99.27.
Effects of oxiracetam on cholinergic neurons were investigated by biochemical methods. 1) Oxiracetam did not inhibit 3H-QNB binding in the cerebral cortex and hippocampus. 2) In the 3H-QNB binding study, oxiracetam did not change the inhibition-concentration curve for the muscarinic agonist carbachol and had no effect on GppNHp-induced inhibition of oxotremorine binding. 3) Oxiracetam (10-100 microM) enhanced K(+)-induced ACh release from slices of rat hippocampus. 4) In the in vitro perfusion studies, oxiracetam (10-100 microM), but not aniracetam and piracetam, enhanced choline-acetyltransferase (ChAT) activity in the hippocampal slices. 5) Repeated administration of oxiracetam (100 or 500 mg/kg, p.o., once daily) to old rats significantly enhanced ChAT activities in the cerebral cortex, hippocampus and striatum, while it did not influence the Bmax and Kd for 3H-QNB binding in the hippocampus. 6) Oxiracetam did not affect the acetylcholinesterase activity in mouse brain homogenate. These results suggest that oxiracetam enhances precholinergic functions.
采用生化方法研究了奥拉西坦对胆碱能神经元的作用。1）奥拉西坦不抑制大脑皮质和海马体中3H-QNB的结合。2）在3H-QNB结合研究中，奥拉西坦不改变毒蕈碱激动剂卡巴胆碱的抑制浓度曲线，且对GppNHp诱导的氧化震颤素结合抑制无影响。3）奥拉西坦（10 - 100微摩尔）增强了钾离子诱导的大鼠海马体切片中乙酰胆碱的释放。4）在体外灌注研究中，奥拉西坦（10 - 100微摩尔）而非阿尼西坦和吡拉西坦增强了海马体切片中胆碱乙酰转移酶（ChAT）的活性。5）对老年大鼠反复口服给予奥拉西坦（100或500毫克/千克，每日一次）可显著增强大脑皮质、海马体和纹状体中ChAT的活性，而不影响海马体中3H-QNB结合的Bmax和Kd。6）奥拉西坦不影响小鼠脑匀浆中的乙酰胆碱酯酶活性。这些结果表明奥拉西坦增强了胆碱能前体功能。
