Comparative Analysis of Experimental Pharmacokinetics of New Neurotropic Peptides

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S.S. Boyko
V.P. Zherdev
R.V. Shevchenko
O.G. Gribakina


Experimental pharmacokinetics of new pharmacologically active peptides, modified analogues of endogenous neuropeptides, has been investigated in rats and rabbits. The study icluded 3 new drugs: (i) the nootropic drug noopept (phenylacetyl-prolyl-glycine ethyl ester); (ii) dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) – the antipsychotic with positive mnemotropic action; (iii) compound GB-115 – selective anxiolytic (phenylhexanoyl-prolyl-tryptophan amide). Differences in pharmacokinetics and biotransformation of the studied drugs depended on their structural features. The ether derivatives noopept and dilept underwent intensive metabolism by rat gastrointestinal esterases and peptidases with the formation of active metabolites. Being an amide, the compound GB-115 was more resistant to the enzymatic effects of peptidases and was detected for a longer period in the blood of experimental animals. In rabbits the studied compounds were less exposed to the enzymatic action by gastrointestinal peptidases, and were detected plasma of rabbits for a longer period. The higher stability of the compounds studied in rabbits may be attributed not only to the structural features of the studied dipeptides, but also to differences in the activity of the enzymatic systems of the gastrointestinal tract participating in their metabolism, as well as differences in the rate of hepatic and renal blood flow in rats and rabbits.

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Boyko, S., Zherdev, V., Shevchenko, R., & Gribakina, O. (2019). Comparative Analysis of Experimental Pharmacokinetics of New Neurotropic Peptides. Biomedical Chemistry: Research and Methods, 2(1), e00092.


  1. Firsov, A.A., Zherdev, V.P., Portnoji, Yu.A., Kolyvanov, G.B., Litvin, A.A., Barmanov, E.Yu. (2013) Guidelines for conducting preclinical studies of drugs. Part One (A.N. Mironov, N. D. Bunatyan, ed.), GRIF and Co., Moscow, pp. 843-853.
  2. Boyko, S.S., Zherdev, V.P., Dvoryaninov, A.A., Gudasheva, T.A., Ostrovskaya, R.U. (1997) Pharmacokinetics of a dipeptide analogue of piracetam with the nootropic activity GVS-111 and its main metabolites. Exper. and Clin. Pharmacol., 60(2), 53-55.
  3. Boyko, S.S., Zherdev, V.P., Korotkov, S.A., Gudasheva, T.A., Ostrovskaya, R.U. (2001) Pharmacokinetics of new potentially active dipeptide preparation GVS-111 and its metabolites in the rat brain. Chemical-Farm. Journal, 35(9), 11-13. DOI
  4. Shevchenko, R.V., Litvin, A.A., Kolyvanov, G.B., Boyko, S.S., Zherdev, V.P. (2014) Specific features in pharmacokinetics of the original neuroleptic dilept in animals and humans Exper. and Clin. Pharmacol, 77(7), 23-27.
  5. Zherdev, V.P., Boyko, S.S., Mesonzhnik, N.V. (2009) Experimental pharmacokinetics of the pharmacological drug Dilept. Exper. and Clin. Pharmacol., 22(3), 16-21.
  6. Boyko, S.S., Kolyvanov, G.B., Zherdev, V.P., Gudasheva, T.A., Kiryanova, E.P., Seredenin, S.B. (2007) Experimental study of pharmacokinetics of tryptophan-containing dipeptide GB-115. Bull. Exper. Biol. and Medicine, 144(9), 285-288. DOI
  7. Zherdev, V.P., Boyko, S.S., Blynskaya, E.V., Turchinskaya, K.G., Gudasheva, T.A., Ivannikova, E.V. (2015) Preclinical study of the pharmacokinetics of the new anxiolytic dipeptide nature GB-115. Pharmacokinetics and Pharmacodynamics, 1, 55-59.
  8. Kolik L.G., Zherdev V.P., Boyko S.S. et al. (2016). Experimental pharmacokinetics and pharmacodynamics of the substance dipeptide anxiolytic GB-115. Exper. and clin. Pharmacol., 11, 42-46.
  9. Klusha V.E. Peptides are regulators of brain function. Zinatne, Riga. 1984
  10. Aronin N., Garrawaj, R.W., Ferris, C.G. (1982). The stability and metabolism of intravenosuusly administrated neurotensine in the rats. Peptides, 3(4), 637-642.
  11. Herranz, R. (2003). Cholecystokinin antagonists; Pharmacological and Therapeutic potencial. Med. Res. Rev. 23(5), 559-605.
  12. Ostrovskaya, R.U., Gudasheva, T.A., Voronina, T.A., Seredinin, S.B. (2002). The original nootropic and neuroprotective drug noopept. Exper. and Clin. Pharmacol., 63(5), 66-72. DOI
  13. Gorelov, P.I., Ostrovskaya, R.U., Sazonova, N.M. (2013) Evaluation of the pro-cognitive effect of dilept and its main metabolite, GZR-125, in the object recognition test in rats. Exper. and Clin. Pharmacol., 76(7), 3-5. DOI
  14. Anand B.S., Katragadda S., Mitra A.K. (2004) Pharmacokinetics of novel dipeptide ester prodrugs of acyclovir after oral administration: intestinal absorbtion and liver metabolism. J. Pharmacol Exp Ther. 311(2): 659-671 DOI
  15. Bahar F.G., Ohura K., Ogihara T., Imai T. (2012) Species difference of esterase expression and hydrolase activity in plasma. J.Pharm.Sci. 101(10): 3979-88 DOI
  16. Shimada, T., Mimura, M., Inoue, K, Nakamura, S, Oda, H, Ohmori, S, Yamazaki, H. (1997) Cytochrome P-450-dependent animal species including rats, guinea pigs, dogs, monkeys and humans. Archiv. Toxicol. 71(6), 401-408.
  17. Zherdev, V.P., Shevchenko, R.V., Kolyvanov, G.B., Litvin, A.A. (2017) Interspecific differences in the pharmacokinetics of drugs. Exper. and clin. Pharmacol., 80(9), 62-689.
  18. Zherdev, V.P., Boyko, S.S., Shevchenko, R.V., Bochkov, P.O., Gribakina, O.G., Ruskin, S.Yu. (2018) The role of interspecific pharmacokinetics studies in the creation of new peptide drugs. Pharmacokinetics and Pharmacodynamics, (1), 3–23 .