van der Laan J W, Weick G, van Bleek G
Biochem Pharmacol. 1985 Nov 1;34(21):3789-94. doi: 10.1016/0006-2952(85)90426-5.
Four inhibitors of gamma-aminobutyric acid transaminase (GABA-T) were investigated together with respect to their effects on hole-board exploration and temperature and the relation with effects on quasi-morphine-abstinence behaviour induced by dipropylacetate (DPA) in rats. Amino-oxyacetic acid (AOAA), gamma-acetylenic-GABA (GAG), gamma-vinyl-GABA (GVC) and ethanolamine-O-sulfate (EOS) were found to reduce hole-board exploration especially in the higher doses used, although the time-course of the effect was different for the compounds. For EOS and GVG the decrease in hole-board exploration paralleled a strong hypothermic effect. The compounds AOAA and GAG exerted a less and more transient hypothermic effect. However, the decrease in hole-board exploration did not fall in with this decrease in temperature. AOAA and GAG were found to decrease DPA-induced body shakes and locomotor activity, while GVG and EOS had no effect on body shakes and transient effects but opposite to each other, on locomotor activity. The efficacy of the GABA-T-inhibitors was measured biochemically, and the influence on the activity of glutamate decarboxylase (GAD) was also determined. AOAA and GAG were found to be strong inhibitors of GABA-T whereas the other two compounds were less efficient in the used doses. In addition AOAA and GAG influenced the activity of GAD strongly, while using GVG only a small decrease was found. The results suggest that the anti-quasi-withdrawal, the sedative and the hypothermic effects are not related to each other nor related to an effect on GABA-T. The suppressive effects on quasi-withdrawal body shakes, however, could be related to the inhibition of GAD and a hypothesis involving a compartmentalized action of DPA on GABA-metabolism has been proposed.
研究了四种γ-氨基丁酸转氨酶（GABA-T）抑制剂，观察它们对大鼠在空板试验中的探索行为、体温的影响，以及与二丙基乙酸（DPA）诱导的准吗啡戒断行为的关系。发现氨基氧乙酸（AOAA）、γ-乙炔基-GABA（GAG）、γ-乙烯基-GABA（GVC）和乙醇胺-O-硫酸盐（EOS）会减少空板试验中的探索行为，尤其是在使用较高剂量时，尽管不同化合物的作用时间进程有所不同。对于EOS和GVG，空板试验探索行为的减少与强烈的体温过低效应平行。化合物AOAA和GAG产生的体温过低效应较弱且更短暂。然而，空板试验探索行为的减少与体温下降并不一致。发现AOAA和GAG可减少DPA诱导的身体颤抖和运动活动，而GVG和EOS对身体颤抖无影响，对运动活动有短暂影响，但方向相反。通过生化方法测定了GABA-T抑制剂的效力，还确定了它们对谷氨酸脱羧酶（GAD）活性的影响。发现AOAA和GAG是GABA-T的强抑制剂，而其他两种化合物在所使用的剂量下效果较差。此外，AOAA和GAG对GAD的活性有强烈影响，而使用GVG时仅发现有小幅下降。结果表明，抗准戒断、镇静和体温过低效应彼此无关，也与对GABA-T的作用无关。然而，对准戒断身体颤抖的抑制作用可能与GAD的抑制有关，并且已经提出了一个涉及DPA对GABA代谢的区室化作用的假说。
