The anxiolytic and antidepressant activities of complex preparations divaza and brizantin containing antibodies to brain-specific protein S100 were estimated using Vogel conflict test and Nomura forced swimming test. Course treatment (5 days) of brizantin in a dose of 2.5 ml/kg and divaza in a dose of 7.5 ml/kg significantly increased punished drinking in the Vogel conflict test in comparison with the control. Both drugs also improved general emotional behavior during training prior to the test procedure. Brizantin and divaza in a dose of 7.5 ml/kg increased the number of wheel revolutions in the Nomura forced swimming test in comparison with the control; the effect of divaza was more pronounced. High correlation coefficients between the number of wheel revolutions during the first and second 5-min sessions are also indicative of antidepressant action of divaza and brizantin.

A series of new 1,2,4,5-tetrahydro-3H-pyrrolo[1,2-a][1,4]diazepin-3-one derivatives were synthesized from widely available furfurol, 3-aminopropionic acid, and amines. The antidepressant and anxiolytic properties of the obtained compounds were investigated. Results of Nomura and Porsolt forced swimming tests showed that some of the compounds exhibited antidepressant activity at doses of 7 μmol/kg (1.1 – 2.2 mg/kg). Use of the Vogel conflict test showed that several compounds possessed anxiolytic activity at the same doses. The activities of the most active compounds exceeded those of the reference drugs, antidepressant amitriptyline and daily tranquilizer medazepam, at doses of 10 mg/kg.

A series of new 1,2,4,5-tetrahydro-3 H -pyrrolo[1,2- a ][1,4]diazepin-3-one derivatives have been synthesized using widely available furfural, 3-aminopropionic acid, and amines. Antidepressant and anxiolytic properties of the obtained compounds were investigated. Results of the Nomura and Porsolt forced swimming tests showed some of the synthesized compounds to exhibit antidepressant activity in doses of 7 μmol/kg (1.1 – 2.2 mg/kg). Using the Vogel conflict test, several compounds were shown to possess anxiolytic activity in the same doses. The effects of most active compounds exceeded the activity of reference preparations — the antidepressant amitriptyline and daily tranquilizer medazepam in doses of 10 mg/kg.

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.

The behavioral and neurochemical effects of synthetic dipeptide fragment GSB-106 of BDNF, administered in a single dose of 0.1 mg/kg (i.p.), have been studied in comparison to amitriptyline (10 mg/kg, i.p.) on the Nomura depressive state model employing forced-rotating-wheel swim test (FST) in Wistar rats. Amitriptyline is known to increase both the number of wheel turns and the index of correlation between the number of turns in the first and last 5-min intervals of observation. It is established that GSB-6 produces a pronounced antidepressant effect comparable to that of amitriptyline, while not influencing the content of monoamines in brain structures of intact (non-depressive) rats. HPLC study showed that GSB-106 increased the complex parameters of dopamine metabolism (DOPAC/DA and HVA/DA) in nucleus accumbens and striatum of rats undergoing FST as compared to the same indices in intact animals. A decrease in the norepinephrine (NE) content by 50% was detected in striatum and hippocampus of rats with depression model. GSB-106 to significantly increased the number of wheel turnings and prevent the elevation of DA and its metabolite DOPAC levels in hypothalamus. A decrease in 5-HIAA (serotonin metabolite) content was also detected in frontal cortex and hypothalamus.