European Journal of Drug Metabolism and Pharmacokinetics

, Volume 22, Issue 3, pp 245–252

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

  • T. A. Gudasheva
  • S. S. Boyko
  • R. U. Ostrovskaya
  • T. A. Voronina
  • V. K. Akparov
  • S. S. Trofimov
  • G. G. Rozantsev
  • A. P. Skoldinov
  • V. P. Zherdev
  • S. B. Seredenin
Article

DOI: 10.1007/BF03189814

Cite this article as:
Gudasheva, T.A., Boyko, S.S., Ostrovskaya, R.U. et al. European Journal of Drug Metabolism and Pharmacokinetics (1997) 22: 245. doi:10.1007/BF03189814

Summary

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.

Keywords

Cognitive enhancerpiracetam analogueN-phenylacetylprolylglycine ethyl ester metabolismcyclo-prolylglycinegas chromatography-mass spectrometry

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • T. A. Gudasheva
    • 2
  • S. S. Boyko
    • 2
  • R. U. Ostrovskaya
    • 2
  • T. A. Voronina
    • 2
  • V. K. Akparov
    • 1
  • S. S. Trofimov
  • G. G. Rozantsev
    • 2
  • A. P. Skoldinov
    • 2
  • V. P. Zherdev
    • 2
  • S. B. Seredenin
    • 2
  1. 1.State Institute of Genetic and Selection of Industrial MicroorganismsMoscowRussia
  2. 2.Chemistry Department, Institute of PharmacologyRussian Academy of Medical ScienceMoscowRussia