Biomedical Chemistry: Research and Methods 2019, 2(1), e00092

Comparative Analysis of Experimental Pharmacokinetics of New Neurotropic Peptides

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

Zakusov Institute of Pharmacology 8 Baltiyskaya str., Moscow, 125315 Russia; *e-mail: svboyko@gmail.com

Keywords: neurotropic peptide drugs; comparison of experimental pharmacokinetics; metabolism of peptide drugs

DOI:10.18097/BMCRM00092

The whole version of this paper is available in Russian.

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
Figure 1. Experiment design (rats).
Figure 2. Experiment design (rabbits).
Figure 3. Noopept metabolism scheme.

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Table 1. Pharmacokinetic parameters of noopept, dilept and their active metabolites (CPG and M-1) and compound GB-115 in rats after a single oral administration of drug substances.

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Table 2. Pharmacokinetic parameters of noopept, dilept and their active metabolite M-1 and compound GB-115 in rabbits after a single oral administration of drug substances.

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