Carmona E, Gomes C, Trolin G
Naunyn Schmiedebergs Arch Pharmacol. 1980 May;312(1):51-5. doi: 10.1007/BF00502574.
The accumulation of GABA in the cerebellum and medulla oblongata-pons of rats has been studied after inhibition of GABA-T (EC 2.6.1.19) by different doses of AOAA. It was found that intraperitoneal (i.p.) injections of AOAA were, at least during the first hour after injection, much less effective than intravenous (i.v.) injections probably due to poor absorption i.p. After i.v. injection, AOAA caused a maximal accumulation of GABA in the cerebellum at a dose of 50 mg/kg. This maximal effect was virtually unchanged up to a dose of 150 mg/kg (the highest dose tested i.v.). If GAD (EC 4.1.1.15) was inhibited by 3-mercaptopropionic acid 30 min after AOAA (90 mg/kg i.v.) the GABA level was stable for at least another 30 min. The rate of GABA accumulation in the cerebellum during the first 15 min after AOAA (50-150 mg/kg i.v.) was 0.086 mumol/g/min and thereafter 0.034 mumol/g/min. It is concluded that AOAA in vivo in a wide dose range inhibits GABA-T almost 100% without affecting GAD to any great extent, and that the onset of action is rapid after i.v. but not after i.p. injection.
在通过不同剂量的氨氧乙酸（AOAA）抑制大鼠小脑和延髓-脑桥中的γ-氨基丁酸转氨酶（GABA-T，EC 2.6.1.19）后，对GABA在这些部位的蓄积情况进行了研究。结果发现，腹腔注射AOAA至少在注射后的第一个小时内，其效果远不如静脉注射，这可能是由于腹腔注射吸收较差所致。静脉注射后，AOAA在剂量为50mg/kg时可使小脑内的GABA蓄积达到最大值。直至剂量达到150mg/kg（静脉注射测试的最高剂量），这种最大效应实际上没有变化。如果在AOAA（静脉注射90mg/kg）30分钟后用3-巯基丙酸抑制谷氨酸脱羧酶（GAD，EC 4.1.1.15），GABA水平至少在接下来的30分钟内保持稳定。在AOAA（静脉注射50 - 150mg/kg）后的前15分钟内，小脑内GABA的蓄积速率为0.086μmol/g/min，此后为0.034μmol/g/min。结论是，体内的AOAA在很宽的剂量范围内几乎可100%抑制GABA-T，而对GAD没有太大影响，并且静脉注射后起效迅速，但腹腔注射后则不然。
