[Behavioral and neuroreceptor effects of the racetam derivative GIZh-290 in mouse experimental attention deficit model]. / Povedencheskie i neiroretseptornye éffekty proizvodnogo ratsetama GIZh-290 s ispol'zovaniem éksperimental'noi modeli defitsita vnimaniia.

Behavioral and neurochemical effects of the new racetam derivative GIZh-290 were studied in a mouse attention deficit model (the ED-Low animals subpopulation selected during preliminary behavioral typing in the "closed enriched cross maze" test). Subchronic administration of GIZh-290 (1 mg/kg, 3 mg/kg and 5 mg/kg, intraperitoneally, for 6 days), increased the initially low level of attention in ED-Low animals; the highest selectivity was observed at a dose of 3 mg/kg. Radioligand analysis showed that at this dose, the drug changed density (Bmax) of D2 and GABAB receptors as markers in the pre-frontal cortex of the ED-Low subpopulation to Bmax values observed in the ED-High subpopulation. In the prefrontal cortex of the ED-Low rodents treated with GIZh-290 in dose of 3 mg/kg, there was a normalization of tissue concentrations of both dopamine itself (DA) and its intra- and extracellular metabolites (DOPA/DA and HVA/DA). The obtained results indicate the effectiveness of the studied drug for pharmacotherapy of attention deficit in experimental modeling and impact on potential molecular targets identified in the study.

[Influence of pantogam and atomoxetine on attention stability and distribution of dopamine D2 and GABAB receptors in the attention deficit mouse model]. / Vliianie pantogama i atomoksetina na ustoichivost' vnimaniia i raspredelenie dofaminovykh D2 i GAMKV-retseptorov u myshei s model'iu defitsita vnimaniia.

The closed enriched cross maze test was employed as a new experimental model of the attention deficit disorder (ADD) for evaluation of the behavioral and neurochemical effects of the nootropic drug pantogam (100 mg/kg, intraperitoneally) and atomoxetine hydrochloride (3 mg/kg, intraperitoneally) administered subchronically to CD-1 outbred mice. Two subpopulations of rodents differed spontaneously in attention to enriched compartments (ED-Low and ED-High), were estimated on the basis of time spent by the mice in the empty or enriched compartments. The ED-Low and ED-High mice insignificantly differed in parameters associated with anxiety, exploratory efficacy and motor activity. Subchronic administration of both drugs in selected doses produced corrective effect on animal behavior seen as a selective increase in the ED-ratio values in the ED-Low subpopulation. Differences in the distribution of dopamine D2 and GABAB receptors (Bmax) between placebo-treated ED-Low and ED-High mice were found in the prefrontal cortex using the radioligand binding method. The neuroreceptor effects of atomoxetine were seen in prefrontal cortex of ED-Low mice as decrease in the Bmax values of D2 receptors by 14%. Pantogam in the prefrontal cortex of ED-Low subpopulation showed a decrease in the Bmax values of D2 receptors by 22% and an increase for GABAB receptors by 44%. Therefore, subchronic administration of pantogam had a positive corrective effect on the behavior parameters and the density of the studied receptor subtypes in animals with severe attention deficit.

[Proteolysis of horse blood serum proteins at various stages of antitoxic sera production by the Diaferm-3 method]. / O proteolize belkov syvorotki krovi loshadi na razlichnykh stadiiakh polucheniia antitoksicheskikh syvorotok po metodu "Diaferm-3".

When preparing antitoxic sera by the method "Diaferm-3", it was found that proteolysis of the horse blood serum occurs not only at the fermentation step (pepsin treatment at the enzyme-substrate ratio of 1/10, t 20-23 degrees for an hour at pH 3.3 and for the next hour at pH 4.2), but also at the heat treatment step (45 min at pH 4.3, t 56-58 degrees in the presence of ammonium sulfate at a concentration of 140-145 g/l). At the fermentation step immunoglobulins do not split completely into F(ab')2 fragments, 40% of the antitoxic activity being lost at this step. Some ballast proteins--albumin, fibrinogen, etc.--quickly split up into peptides, while other proteins undergo only limited proteolysis. Structural destabilization of serum proteins during thermodenaturing is favorable for the pepsin action and provides for a complete conversion of immunoglobulins to F(ab')2 and Fab' fragments. At this step about 15% of the antitoxic activity is additionally lost. Thus, proteolysis at the thermodenaturation step is an essential part of the "Diaferm-3" process.