Gudasheva T A, Boyko S S, Ostrovskaya R U, Voronina T A, Akparov V K, Trofimov S S, Rozantsev G G, Skoldinov A P, Zherdev V P, Seredenin S B
Institute of Pharmacology, Russian Academy of Medical Science, Moscow, Russia.
Eur J Drug Metab Pharmacokinet. 1997 Jul-Sep;22(3):245-52. doi: 10.1007/BF03189814.
The metabolism of a new piracetam analogue, the dipeptide cognitive enhancer N-phenylacetyl-L-prolylglycine ethyl ester (GVS-111) was studied in vivo. GVS-111 itself was not found in rat brain 1 h after 5 mg/kg i.p. administration up to limit of detection (LOD) under high performance liquid chromatography (HPLC) conditions. Three substances corresponding to the three possible GVS-111 metabolites, namely phenylacetic acid, prolylglycine and cyclo-prolylglycine, were found in experimental rat brain samples as well as in controls using HPLC, gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) methods. Only cyclo-prolylglycine concentration increased (2.5-fold) 1 h after GVS-111 administration. Cyclo-prolylglycine formation from GVS-111 in the presence of plasma and brain enzymes was shown in vitro. These data could be considered as evidence that GVS-111 is prodrug which converts in the body to cyclo-prolylglycine, and which is identical to the endogenous cyclopeptide that produces the nootropic activity.
对一种新的吡拉西坦类似物——二肽认知增强剂N-苯基乙酰基-L-脯氨酰甘氨酸乙酯（GVS-111）进行了体内代谢研究。在5mg/kg腹腔注射后1小时，大鼠脑中未检测到GVS-111本身，在高效液相色谱（HPLC）条件下检测限以下未发现其存在。使用HPLC、气相色谱（GC）和气相色谱-质谱联用（GC-MS）方法，在实验大鼠脑样本以及对照样本中发现了三种与GVS-111三种可能代谢物相对应的物质，即苯乙酸、脯氨酰甘氨酸和环脯氨酰甘氨酸。仅在给予GVS-111后1小时，环脯氨酰甘氨酸浓度增加（2.5倍）。体外实验表明，在血浆和脑酶存在的情况下，GVS-111可形成环脯氨酰甘氨酸。这些数据可被视为证据，表明GVS-111是一种前药，在体内可转化为环脯氨酰甘氨酸，且与产生促智活性的内源性环肽相同。
