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- W2912756823 abstract "Involvement of BDNF in the regulation of neuroplasticity and neurogenesis in the hippocampus, impairment of which underlies the pathophysiology of depression, makes this endogenous protein a promising object for the development of new-generation antidepressants with a neurophysiologically based mechanism of action. A low-molecular-weight BDNF mimetic, GSB-106 (a substituted dimeric dipeptide, bis-(N-monosuccinyl- L-seryl-L-lysine) hexamethylenediamide), was designed and synthesized at the Zakusov Institute of Pharmacology. GSB-106 was found to activate BDNF-specific TrkB receptors and their main post-receptor signaling pathways MAPK/ERK and PI3K/AKT. GSB-106 exhibited pronounced antidepressant activity in a rodent test battery at a dose of 0.1 to 1.0 mg/kg administered intraperitoneally. Because oral administration is preferable in the treatment of depression, which is associated with a prolonged duration and outpatient character of pharmacotherapy, we examined the antidepressant properties of GSB-106 administered orally as a pharmaceutical substance (PS) and in tablet dosage form (TDF). In the study, we used the Porsolt forced swim test in rats; a conventional antidepressant, Amitriptyline, was used as a reference drug. The antidepressant activity of GSB-106 was found to retain upon oral administration and to manifest at doses of 0.5-5.0 mg/kg for PS and 0.01-5.0 mg/kg for TDF. The effective dose of TDF was 50-fold lower than that of PS, and the efficacy of tableted GSB-106 exceeded that of Amitriptyline, the gold standard in antidepression care. Therefore, GSB-106, both as a substance and as a tablet dosage form, exhibits antidepressant activity when administered orally, which makes it a promising antidepressant agent, the first in the class of BDNF mimetics." @default.
- W2912756823 created "2019-02-21" @default.
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- W2912756823 date "2018-09-15" @default.
- W2912756823 modified "2023-10-05" @default.
- W2912756823 title "Antidepressant Effect of an Orally Administered Dipeptide Mimetic of the Brain-Derived Neurotrophic Factor" @default.
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- W2912756823 doi "https://doi.org/10.32607/20758251-2018-10-3-81-83" @default.
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