The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine

Eur J Drug Metab Pharmacokinet. Jul-Sep 1997;22(3):245-52. doi: 10.1007/BF03189814.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Chromatography, High Pressure Liquid
  • Dipeptides / chemistry
  • Dipeptides / metabolism*
  • Male
  • Mass Spectrometry
  • Neuropeptides / chemistry
  • Neuropeptides / metabolism
  • Nootropic Agents / chemistry
  • Nootropic Agents / metabolism*
  • Piracetam / pharmacology
  • Rats

Substances

  • Dipeptides
  • Neuropeptides
  • Nootropic Agents
  • prolylglycine
  • ethyl phenylacetyl-Pro-Gly
  • Piracetam