Antidepressant Effect of Dimeric Dipeptide GSB-106, an Original Low-Molecular-Weight Mimetic of BDNF

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.

Effect of the fragrance inhalation of essential oil from Asarum heterotropoides on depression-like behaviors in mice

“…Pharmacologically, a variety of anti-depressants and related-compounds with potential anti-depressant activity reduce the duration of immobility in the FST and TST [ 22 , 23 ]. Therefore, the reduction of immobility is the important factor to develop the pharmacological approaches to the treatment of depression-like behaviors in experimental designs.…”

Dimeric Dipeptide Mimetics of NGF and BDNF Are Promising Agents for Post-Stroke Therapy

“…Furthermore BDNF-stimulated MAPK/ERK pathway involved in the regulation of neurogenesis and neuroplasticity, which are the two types of cellular events that take part in recovery after a stroke. Previously GSB-106 was shown to stimulate hippocampal neurogenesis in adult stressed mice [26].…”

The BDNF Loop 4 Dipeptide Mimetic Bis(N-monosuccinyl-L-seryl-L-lysine)hexamethylenediamide Is Active in a Depression Model in Mice after Acute Oral Administration

“…On day 11, these groups were single orally administered with a 1% starch solution (control group [no stress]), GSB-106 (the group "GSB-106 [without stress]") or amitriptyline (group "amitriptyline [without stress]") in a 1% starch solution, respectively. The dose of GSB-106 was selected based on previously conducted experiments [12]; the one of amitriptyline was based on literature data [17]. The sucrose preference test was performed on day 13.…”

“…GSB-106 demonstrated antidepressant activity at intraperitoneal (i.p.) (0.1-1.0 mg/kg) and oral (0.5-5.0 mg/kg) administration in a number of rodent tests [11,12]. GSB-106 was also shown to stimulate neurogenesis and synaptogenesis in mouse hippocampus [13,14].…”