THE MAJOR METABOLITE OF DIPEPTIDE PIRACETAM ANALOG GVS-111 IN RAT-BRAIN AND ITS SIMILARITY TO ENDOGENOUS NEUROPEPTIDE CYCLO-L-PROLYLGLYCINE

The metabolism of a new piracetam analogue, the dipeptide cognitive en hancer N-phenylacetyl-L-prolylglycine ethyl ester (GVS-111) was studie d 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 perform ance liquid chromatography (HPLC) conditions. Three substances corresp onding to the three possible GVS-111 metabolites, namely phenylacetic acid, prolylglycine and cyclo-prolylglycine, were found in experimenta l rat brain samples as well as in controls using HPLC, gas chromatogra phy (GC) and gas chromatography-mass spectrometry (GC-MS) methods. Onl y 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 c ould be considered as evidence that GVS-111 is prodrug which converts in the body to cyclo-prolylglycine, and which is identical to the endo genous cyclopeptide that produces the nootropic activity.