Antidepressant Effect of Dimeric Dipeptide GSB-106, an Original Low-Molecular-Weight Mimetic of BDNF
- Authors: Seredenin S.B.1, Voronina T.A.1, Gudasheva T.A.1, Garibova T.L.1, Molodavkin G.M.1, Litvinova S.A.1, Elizarova О.A.1, Poseva V.I.1
-
Affiliations:
- V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
- Issue: Vol 5, No 4 (2013)
- Pages: 105-109
- Section: Research Articles
- Submitted: 17.01.2020
- Published: 15.12.2013
- URL: https://actanaturae.ru/2075-8251/article/view/10581
- DOI: https://doi.org/10.32607/20758251-2013-5-4-105-109
- ID: 10581
Cite item
Abstract
A large amount of clinical and experimental data suggest the involvement of neurotrophins, in particular the brain-derived neurotrophic factor (BDNF), in depression pathogenesis. However, the therapeutic use of BDNF is limited because of its instability in biological fluids, poor blood-brain barrier (BBB) permeability, and the presence of side effects. A low-molecular-weight mimetic GSB-106, which is a substituted dimeric dipeptide bis(N-monosuccinyl-L-seryl-L-lysine)hexamethylenediamide, was designed and synthesized based on the BDNF fourth loop structure at the V.V. Zakusov Institute of Pharmacology (RAMS). GSB-106 was found to exhibit an antidepressant activity in various models of depressive-like state when administered intraperitoneally to outbred mice and rats. An effect for the substance, when administered daily for 4-5 days, was detected in the Porsolt forced swimming test (0.1 and 1.0 mg/kg) and in the tail suspension test in mice (1.0 and 1.5 mg/ kg). An effect for GSB-106 at doses of 0.1 and 0.5 mg/kg was observed after a single application in experiments on rats in the Nomura water wheel test. The obtained evidence supports the hypothesis on the involvement of BDNF in the pathogenesis of various depression conditions, thus opening prospects for searching for new original antidepressants.
About the authors
S. B. Seredenin
V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
Email: t_garibova@mail.ru
Russian Federation
T. A. Voronina
V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
Email: t_garibova@mail.ru
Russian Federation
T. A. Gudasheva
V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
Email: t_garibova@mail.ru
Russian Federation
T. L. Garibova
V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
Author for correspondence.
Email: t_garibova@mail.ru
Russian Federation
G. M. Molodavkin
V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
Email: t_garibova@mail.ru
Russian Federation
S. A. Litvinova
V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
Email: t_garibova@mail.ru
Russian Federation
О. A. Elizarova
V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
Email: t_garibova@mail.ru
Russian Federation
V. I. Poseva
V.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences
Email: t_garibova@mail.ru
Russian Federation
References
- // 10 facts about the global burden of disease. // WHO Bulletin. 2008, url www.who.int/features/factfiles/global_burden/ ru/index.html
- Sartorius N. // Med. Res. 2001, V.1, P.20-21
- Wittchen H.U. // V.M. Bekhterev Review of Psychiatry and Medical Psychology. 2005, №4, P.42-46
- Angelucci F., Mathe A.A., Aloe L. // Progress in Brain Research. 2004, V.146, P.151-165
- Yu H., Chen Z.Y. // Acta Pharmacologica Sinica. 2011, V.32, P.3-11
- Neto F.L., Borges G., Torres-Sanchez S., Mico J.A., Berrocoso E. // Current Neuropharmacology. 2011, №9, P.530-552
- Karege F., Perret G., Bondolfi G., Schwald M., Bertschy G., Aubry J.M. // Psychiatry Res. 2002, V.109, P.143-148
- Chen B., Dowlatshahi D., MacQueen G.M., Wang J.F., Young L.T. // Biological Psychiatry 2001, V.50, P.260-265
- Siuciak J.A., Lewis D.R., Wiegand S.J., Lindsay R.M. // Pharmacol. Biochem. Behav. 1997, V.56, P.131-137
- Shirayama J., Chen A.C., Nakagawa S., Russel R.S., Duman R.S. // J. Neurosci. 2002, V.22, P.3251-3261
- Govindarajan A., Rao B.S.S., Nair.D I.O., Trinh M., Mawjee N., Tonegawa S., Chattarji S. // Proc. Natl. Acad. Sci. USA 2006, P.13208-13213
- Siuciak J.A., Altar C.A., Wiegand S.J., Lindsay R.M. // Brain Res. 1994, V.663, P.326-330
- O’Leary P.D., Huges R.A. // J. Biol. Chem. 2003, V.278, P.25738-25744
- Massa S.M., Yang T., Xie Y., Shi J., Bilgen M., Joyce J.N., Nehama D., Rajadas J., Longo F.M. // J. Clin. Investigation. 2010, V.120, P.1774-1785
- Seredenin S.B., Gudasheva T.A. // Patent RU S № 2410392 of 16.02.2009 priority. 2011
- Gudasheva T.A., Tarasyuk A.V., Pomogaybo S.V., Logvinov I.O., Povarnina P.Y., Antipova T.A., Seredenin S.B. // Bioorganic Chemistry. 2012, V.38, P.280-290
- Logvinov I.O., Antipova T.A., Gudasheva T.A., Tarasyuk A.V., Antipov P.I., Seredenin S.B. // Bull.Exp.Biol.Med. 2013
- Porsolt B.D., Bertin A., Jalfre M. // Europ. J. Pharmacol. 1978, V.51, P.291-294
- Nomura S., Shimizu J., Kinjo M., Kametani H., Nakazava T. // Eur. J. Pharmacol. 1982, V.83, P.171-175
- Steru L., Chermat R., Thierry B., Simon P. // Psychopharmacology. 1985, V.85, P.367-370
- Molodavkin G.M., Voronina T.A., Mdzinarishvili A.L. // Exp. Cl. Pharm. 1994, V.1, P.3-5
- Schmidt H.D., Duman R.S. // Neuropsychopharmacology. 2010, V.35, P.2378-2391
- Gudasheva T.A., Logvinov I.O., Antipova T.A., Seredenin S.B. // DAS. 2013, V.451, №5, P.577-583