Antidepressant Effect of a Dipeptide Brain-Derived-Neurotrophic-Factor Mimetic (GSB-106) in a Generic Oral Dosage Form

Таллерова, Анна Вадимовна; Povarnina, P. Yu.; Blynskaya, E. V.; Bueva, V. V.; Alekseev, K. V.; Gudasheva, T. A.; Середенин, С. Б.

doi:10.1007/s11094-018-1828-z

Cited by 3 publications

(3 citation statements)

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“…Forced swimming test [ 20 ] was used to study the mechanism of GSB-106 antidepressant-like action. The test was carried out as described previously [ 11 , 21 ]. The apparatus setup consisted of 5 transparent plastic cylinders 10 cm in diameter and 30 cm in height, separated by black plastic opaque dividers to prevent visual contact of animals during the study.…”

Section: Methodsmentioning

confidence: 99%

Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress

et al. 2021

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A mimetic of the BDNF loop 4, bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, named GSB-106, was designed and synthesized in our scientific group. The compound activated TrkB, MAPK/ERK, PI3K/AKT, and PLCγ in in vitro experiments. In vivo experiments with rodents revealed its antidepressant-like activity in the forced swim and the tail suspension tests at the dose range of 0.1–5.0 mg/kg (i.p., p.o.). However, GSB-106 was not studied in depression models modulating major depression in humans. In the present study, the GSB-106 antidepressant-like activity was revealed in mice at the depression model induced by 28-day social defeat stress with 21-days oral administration (0.1 mg/kg) after stress. At the same time, GSB-106 restored reduced locomotor activity and completely eliminated the anhedonia manifestations. The compound also restored reduced levels of synaptophysin and CREB in the hippocampus. In addition, the Trk receptor antagonist K252A, and the PLC inhibitor U73122, were found to completely block the antidepressant-like activity of GSB-106 in the forced swimming test in mice. Thus, the present results demonstrate the dipeptide BDNF mimetic GSB-106 reversed depressive-like behavior and restored hippocampal neuroplasticity in a rodent depression model. These effects of GSB-106 are probably regulated by TrkB signaling.

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Section: Methodsmentioning

confidence: 99%

Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress

et al. 2021

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“…Experimental groups of at least nine animals each were assigned 23 h after LPS administration and were injected once with GSB-106 at p.o. doses of 0.5, 1.0, and 5.0 mg/kg [10,11]; GML-3 at p.o. doses of 0.5, 1.0, and 5.0 mg/kg [14,15]; and GZK-111 at i.p.…”

Section: Administration Of Gsb-106 Gml-3 and Gzk-111mentioning

confidence: 99%

“…GSB-106 was effective in mice and rats upon peroral (p.o.) administration in the dose range 0.5 -5.0 mg/kg [10,11]. GSB-106 also exhibited antidepressant activity in subchronic and acute social stress models [12,13].…”

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confidence: 99%

Effects of Original Compounds GSB-106, GML-3, and GZK-111 in an Experimental Lipopolysaccharide-Induced Anhedonia Model

et al. 2021

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L-lysine) hexamethylenediamide], a mimetic of the fourth loop of brain-derived neurotrophic factor (BDNF); GML-3 (N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide), a ligand of 18 kDa translocator protein (TSPO); and GZK-111 (N-phenylacetylglycyl-L-proline ethyl ester), a substitute dipeptide that is biotransformed into the neuropeptide cyclo-L-prolylglycine that affects AMPA receptors; were previously revealed at V. V. Zakusov Institute of Pharmacology in experimental models of the depressive state caused by unescapable stress conditions. The present article studied the antidepressant effects of GSB-106, GML-3, and GZK-111 in an inflammatory model of the depressive state induced by lipopolysaccharide (LPS) in male C57Bl/6 mice with an assessment of anhedonia based on the consumption of sucrose solution. LPS in a single dose of 0.5 mg/kg intraperitoneally (i.p.) caused a marked decrease of 39% (p £ 0.01) in the consumption of 1% sucrose solution as compared to the control group. GSB-106 administered perorally at a dose of 0.5 mg/kg 24 h after LPS increased by 20% (p £ 0.05) sucrose consumption reduced by LPS in mice. GML-3 administered once perorally at doses of 0.5 and 1.0 mg/kg increased sucrose consumption by 29 and 21% (p £ 0.01), respectively. GZK-111 administered once i.p. at a dose of 1.0 mg/kg increased sucrose consumption by 17% (p £ 0.05). The obtained data confirmed the antidepressant properties of

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Behavioral Effects of Dimeric Dipeptide BDNF Mimetic GSB-106 in a Rat Model of Depressive-Like State

et al. 2020

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Antidepressant Effect of a Dipeptide Brain-Derived-Neurotrophic-Factor Mimetic (GSB-106) in a Generic Oral Dosage Form

Cited by 3 publications

References 5 publications

Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress

Low-Molecular Weight BDNF Mimetic, Dimeric Dipeptide GSB-106, Reverses Depressive Symptoms in Mouse Chronic Social Defeat Stress

Effects of Original Compounds GSB-106, GML-3, and GZK-111 in an Experimental Lipopolysaccharide-Induced Anhedonia Model

Behavioral Effects of Dimeric Dipeptide BDNF Mimetic GSB-106 in a Rat Model of Depressive-Like State

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