Acta NaturaeActa Naturae2075-8251Acta Naturae Ltd1058110.32607/20758251-2013-5-4-105-109Research ArticleAntidepressant Effect of Dimeric Dipeptide GSB-106, an Original Low-Molecular-Weight Mimetic of BDNFSeredeninS. B.t_garibova@mail.ruVoroninaT. A.t_garibova@mail.ruGudashevaT. A.t_garibova@mail.ruGaribovaT. L.t_garibova@mail.ruMolodavkinG. M.t_garibova@mail.ruLitvinovaS. A.t_garibova@mail.ruElizarovaО. A.t_garibova@mail.ruPosevaV. I.t_garibova@mail.ruV.V.Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences151220135410510917012020Copyright © 2013, Seredenin S.B., Voronina T.A., Gudasheva T.A., Garibova T.L., Molodavkin G.M., Litvinova S.A., Elizarova О.A., Poseva V.I.2013<p>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.</p>BDNFmimeticGSB-106antidepressant activityforced swimming testtail suspension testBDNFмиметикГСБ-106антидепрессивное действиенеизбегаемое плаваниеподвешивание за хвост[[1] // 10 facts about the global burden of disease. // WHO Bulletin. 2008, url www.who.int/features/factfiles/global_burden/ ru/index.html][[2] Sartorius N. // Med. Res. 2001, V.1, P.20-21][[3] Wittchen H.U. // V.M. Bekhterev Review of Psychiatry and Medical Psychology. 2005, №4, P.42-46][[4] Angelucci F., Mathe A.A., Aloe L. // Progress in Brain Research. 2004, V.146, P.151-165][[5] Yu H., Chen Z.Y. // Acta Pharmacologica Sinica. 2011, V.32, P.3-11][[6] Neto F.L., Borges G., Torres-Sanchez S., Mico J.A., Berrocoso E. // Current Neuropharmacology. 2011, №9, P.530-552][[7] Karege F., Perret G., Bondolfi G., Schwald M., Bertschy G., Aubry J.M. // Psychiatry Res. 2002, V.109, P.143-148][[8] Chen B., Dowlatshahi D., MacQueen G.M., Wang J.F., Young L.T. // Biological Psychiatry 2001, V.50, P.260-265][[9] Siuciak J.A., Lewis D.R., Wiegand S.J., Lindsay R.M. // Pharmacol. Biochem. Behav. 1997, V.56, P.131-137][[10] Shirayama J., Chen A.C., Nakagawa S., Russel R.S., Duman R.S. // J. Neurosci. 2002, V.22, P.3251-3261][[11] 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][[12] Siuciak J.A., Altar C.A., Wiegand S.J., Lindsay R.M. // Brain Res. 1994, V.663, P.326-330][[13] O’Leary P.D., Huges R.A. // J. Biol. Chem. 2003, V.278, P.25738-25744][[14] 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][[15] Seredenin S.B., Gudasheva T.A. // Patent RU S № 2410392 of 16.02.2009 priority. 2011][[16] 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][[17] Logvinov I.O., Antipova T.A., Gudasheva T.A., Tarasyuk A.V., Antipov P.I., Seredenin S.B. // Bull.Exp.Biol.Med. 2013][[18] Porsolt B.D., Bertin A., Jalfre M. // Europ. J. Pharmacol. 1978, V.51, P.291-294][[19] Nomura S., Shimizu J., Kinjo M., Kametani H., Nakazava T. // Eur. J. Pharmacol. 1982, V.83, P.171-175][[20] Steru L., Chermat R., Thierry B., Simon P. // Psychopharmacology. 1985, V.85, P.367-370][[21] Molodavkin G.M., Voronina T.A., Mdzinarishvili A.L. // Exp. Cl. Pharm. 1994, V.1, P.3-5][[22] Schmidt H.D., Duman R.S. // Neuropsychopharmacology. 2010, V.35, P.2378-2391][[23] Gudasheva T.A., Logvinov I.O., Antipova T.A., Seredenin S.B. // DAS. 2013, V.451, №5, P.577-583]