The study of the spectrum of pharmacological activity of the new original NT-3 mimetic dipeptide GTS-302
- Authors: Nikiforov D.M.1, Povarnina P.Y.1, Gudasheva T.A.1, Nadorova A.V.1, Kolik L.G.1, Valdman E.A.1, Vakhitova J.V.2, Seredenin S.B.1
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Affiliations:
- Zakusov Research Institute of Pharmacology
- Zakusov Research Institute of Pharmacology, , Russia
- Issue: Vol 23, No 2 (2023)
- Pages: 87-99
- Section: Original research
- Published: 25.08.2023
- URL: https://journals.eco-vector.com/MAJ/article/view/430197
- DOI: https://doi.org/10.17816/MAJ430197
- ID: 430197
Cite item
Abstract
BACKGROUND: The association of the pathogenesis of neurodegenerative diseases, depression, anxiety, and cognitive disorders with the deficit of neurotrophin-3 determines the prospect of creating drugs with a similar mechanism of action. Since the use of full-size neurotrophin-3 is limited by unsatisfactory pharmacokinetic properties, it is relevant to create low-molecular-weight mimetics of neurotrophin-3 that are active when administered systemically. A dimeric dipeptide mimetic of the 4th loop of neurotrophin-3, hexamethylenediamide bis(N-γ-oxibutyryl-L-glutamyl-L-asparagine) GTS-302, which activates TrkC and TrkB receptors, has been developed at the V.V. Zakusov Research Institute of Pharmacology.
AIM: The aim of this study was to investigate the spectrum of pharmacological activity of GTS-302.
MATERIALS AND МETHODS: The pharmacological effects of GTS-302 were investigated following its intraperitoneal administration. The antidepressant-like activity of GTS-302 was studied in the forced swim test in mice after acute and 7-day administration. The anxiolytic and cognitive activity of the dipeptide were studied in the elevated plus maze test in mice and the novel object recognition test in rats after acute administration, respectively. The effect of GTS-302 on pain sensitivity was studied in the hot plate test in mice after acute administration.
RESULTS: It was found that GTS-302 exhibits antidepressant-like activity after acute administration at doses of 0.5, 1.0, 5.0 and 10 mg/kg. After 7-day administration, the antidepressant-like activity of GTS-302 was more pronounced in terms of effect size and statistical significance. The dipeptide GTS-302 at doses of 1.0, 5.0 and 10.0 mg/kg showed anxiolytic and cognitive activity and did not affect pain sensitivity.
CONCLUSIONS: The pharmacological spectrum of the low-molecular-weight mimetic of neurotrophin-3, dipeptide GTS-302, revealed upon systemic administration includes a number of neuropsychotropic effects characteristic of the full-sized neurotrophin. This allows us to consider GTS-302 as a potential neuropsychotropic drug.
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About the authors
Dmitrii M. Nikiforov
Zakusov Research Institute of Pharmacology
Email: mrdmwriter@gmail.com
ORCID iD: 0000-0002-8901-3101
SPIN-code: 7028-8335
Junior Reseаrch Associate at the Laboratory of Peptide Bioregulators of the Department of Medicinal Chemistry
Russian Federation, MoscowPolina Y. Povarnina
Zakusov Research Institute of Pharmacology
Author for correspondence.
Email: povarnina@gmail.com
ORCID iD: 0000-0003-3278-8915
SPIN-code: 5498-6724
Cand. Sci. (Biol.), Senior Reseаrch Associate at the Laboratory of Peptide Bioregulators of the Department of Medicinal Chemistry
Russian Federation, MoscowTatiana A. Gudasheva
Zakusov Research Institute of Pharmacology
Email: tata-sosnovka@mail.ru
ORCID iD: 0000-0002-5185-4474
SPIN-code: 4970-0006
Scopus Author ID: 7003604408
Dr. Sci. (Biol.), Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Medicinal Chemistry
Russian Federation, MoscowAnna V. Nadorova
Zakusov Research Institute of Pharmacology
Email: av-nadorova@mail.ru
ORCID iD: 0000-0002-0463-2190
ResearcherId: R-5731-2018
Reseаrch Associate at the Laboratory of Pharmacological Regulation of Addiction States
Russian Federation, MoscowLarisa G. Kolik
Zakusov Research Institute of Pharmacology
Email: lgkolik@mail.ru
ORCID iD: 0000-0002-9847-8058
SPIN-code: 9126-6922
Dr. Sci. (Biol.), Professor of the Russian Academy of Sciences, Head of the Laboratory of Pharmacological Regulation of Addiction States
Russian Federation, MoscowElena A. Valdman
Zakusov Research Institute of Pharmacology
Email: evaldman@mail.ru
ORCID iD: 0000-0001-9716-499X
SPIN-code: 6806-3799
MD, Dr. Sci. (Med.), Professor, Leading Research Associate at the Laboratory of Psychopharmacology
Russian Federation, MoscowJulia V. Vakhitova
Zakusov Research Institute of Pharmacology, , Russia
Email: juvv73@gmail.com
ORCID iD: 0000-0002-7062-8261
SPIN-code: 1391-4533
Dr. Sci. (Biol.), Corresponding Member of the Russian Academy of Sciences, Director
Russian Federation, MoscowSergey B. Seredenin
Zakusov Research Institute of Pharmacology
Email: seredeninpharm@mail.ru
ORCID iD: 0000-0003-4482-9331
SPIN-code: 3896-4655
MD, Dr. Sсi. (Med.), Professor, Academician of the Russian Academy of Sciences, Head of the Department of Pharmacogenetics
Russian Federation, MoscowReferences
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