[Pharmacokinetics of noopept and its active metabolite cycloprolyl glycine in rats]

Biomed Khim. 2018 Sep;64(5):455-458. doi: 10.18097/PBMC20186405455.
[Article in Russian]

Abstract

The study of the pharmacokinetics of new drugs and the identification of active metabolites is a necessary step for effective and safe use in the clinical practice. It is especially important for peptide drugs due to their enzymatic instability, low bioavailability and poor permeability through the blood-brain barrier (BBB). The role of endogenous neuropeptides containing cyclic amino acids, proline, pyroglutamic acid, and glycine, in the regulation of memory processes is known as terminal peptide fragments. The development of nootropic drugs based on natural neuropeptides with high pharmacological activity and improved pharmacokinetic properties (enzymatic stability, high bioavailability, and good permeability through the BBB) is an important problem of modern neuropsychopharmacology. Developed drugs - representing short (di- and tri-) peptides appear to meet these requirements. In the Zakusov Research Institute of Pharmacology a nootropic agent noopept (N-phenylacetyl-prolyl-L-glycine ethyl ester), was developed and introduced into medical practice, studies of its pharmacokinetics in ratsrevealed that the noopept metabolite found in the rat plasma and brain, cyclo-prolyl-L-glycine (CPG), differed significantly in its pharmacokinetic parameters from noopept, but at the same time it had similar noopept multi-component spectrum of pharmacological action, namely the influence on higher integrative functions of memory.

Issledovanie farmakokinetiki novykh lekarstvennykh sredstv i vyiavlenie aktivnykh metabolitov iavliaetsia neobkhodimym étapom dlia otsenki éffektivnogo i bezopasnogo primeneniia v klinike. Éto osobenno vazhno dlia peptidnykh lekarstvennykh preparatov v sviazi s ikh énzimaticheskoĭ neustoĭchivost'iu, nizkoĭ biodostupnost'iu i plokhoĭ pronitsaemost'iu cherez gemato-éntsefalicheskiĭ bar'er (GÉB). Izvestna rol' éndogennykh neĭropeptidov, soderzhashchikh v kachestve kontsevykh fragmentov tsiklicheskie aminokisloty – prolin, piroglutaminovuiu kislotu, a takzhe glitsina, v reguliatsii protsessov pamiati. Razrabotka nootropnykh lekarstvennykh preparatov na osnove prirodnykh neĭropeptidov s vysokoĭ farmakologicheskoĭ aktivnost'iu i uluchshennymi farmakokineticheskimi svoĭstvami (énzimaticheskoĭ stabil'nost'iu, vysokoĭ biodostupnost'iu i khorosheĭ pronitsaemost'iu cherez GÉB) predstavliaet aktual'nuiu problemu sovremennoĭ neĭropsikhofarmakologii. Ukazannym trebovaniiam udovletvoriaiut razrabatyvaemye na osnove prirodnykh neĭropeptidov s neĭrotropnoĭ aktivnost'iu korotkikh (di- i tri-) peptidov. V NII farmakologii imeni V.V. Zakusova razrabotan i vnedren v meditsinskuiu praktiku v kachestve nootropnogo sredstva noopept – étilovyĭ éfir N-fenilatsetil-prolil-L-glitsina. Pri izuchenii ego farmakokinetiki u krys pokazano, chto obnaruzhennyĭ v plazme i mozge krys metabolit noopepta – tsiklo-prolil-L-glitsin (TsPG) po svoim farmakokineticheskim parametram znachitel'no otlichaetsia ot noopepta, no v to zhe vremia obladaet skhodnym s noopeptom mnogokomponentnym spektrom farmakologicheskogo deĭstviia, a imenno vliianiem na vysshie integrativnye funktsii pamiati.

Keywords: bioavailability; cycloprolyl-glycine (CPG); noopept; pharmacokinetic parameters.

MeSH terms

  • Animals
  • Dipeptides
  • Glycine / metabolism*
  • Nootropic Agents
  • Peptide Fragments
  • Rats

Substances

  • Dipeptides
  • Nootropic Agents
  • Peptide Fragments
  • ethyl phenylacetyl-Pro-Gly
  • Glycine