Fasolato C, Bertazzon A, Previero A, Galzigna L
Institute of Biological Chemistry, University of Padova, Italy.
Pharmacology. 1988;36(4):258-64. doi: 10.1159/000138392.
The effects of 2-pyrrolidone, a cyclic lactam of GABA, were studied on blood and organ levels of 2-pyrrolidone, GABA, glutamic acid, glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T). When administered i.p., the only significant effects observed were increases of brain and liver 2-pyrrolidone. In contrast, regular oral administration for 7 months produced significant increases of GABA and glutamic acid in brain and of glutamic acid alone in liver while GAD decreased in brain and increased in liver; GABA-T was unchanged. A new method for the synthesis of radioactive 2-pyrrolidone was set up and the enzymatic conversion of 2-pyrrolidone to GABA was measured by an original procedure. The results obtained in vitro by this method on the conversion of 2-pyrrolidone to GABA catalyzed by tissue slices, together with the observed inhibition of the GABA-dependent oxygen consumption by 2-pyrrolidone, partially explain the effects of the oral administration.
研究了γ-氨基丁酸的环状内酰胺2-吡咯烷酮对血液及各器官中2-吡咯烷酮、γ-氨基丁酸、谷氨酸、谷氨酸脱羧酶（GAD）和γ-氨基丁酸转氨酶（GABA-T）水平的影响。腹腔注射时，唯一观察到的显著影响是脑和肝脏中2-吡咯烷酮增加。相比之下，连续7个月口服则使脑中γ-氨基丁酸和谷氨酸显著增加，肝脏中仅谷氨酸增加，同时脑中GAD减少而肝脏中GAD增加；GABA-T未发生变化。建立了一种合成放射性2-吡咯烷酮的新方法，并通过一种原始程序测定了2-吡咯烷酮向γ-氨基丁酸的酶促转化。通过该方法在体外获得的组织切片催化2-吡咯烷酮转化为γ-氨基丁酸的结果，以及观察到的2-吡咯烷酮对γ-氨基丁酸依赖性耗氧量的抑制作用，部分解释了口服给药的效果。
