Effects of Gaba Derivatives on Anxious and Compulsive Behavior in Offspring of Rats with Experimental Preeclampsia.

We studied the effects of GABA derivatives on anxious and compulsive behavior of progeny of rats with experimental preeclampsia provoked by replacement of drinking water for 1.8% NaCl solution from the first day of pregnancy to delivery. In comparison with progeny of health rats, the offspring of dams with complicated pregnancy demonstrated high level of anxiety and the development of obsessive-compulsive disorder both at the early (40 and 70 days) and late (6 and 12 months) stages of ontogeny. GABA derivatives succicard, salifen, and phenibut reduced symptoms of experimental preeclampsia in offspring of various age by decreasing the level of anxiety and reducing compulsive behavior. The efficacy of the examined derivatives was similar to that of the reference drug Pantogam.

Survival of Mesenchymal Stem Cells in Different Methods of Nebulization.

We compared survival of bone marrow mesenchymal stem cells after compressor, ultrasound, and mesh nebulization of the cell suspension over 10 min. Viability of stromal cells was best preserved after compressor nebulization (72%). Cell survival after ultrasonic nebulization was significantly lower (20%). After mesh nebulization, no live cells were found. Thus, compressor nebulization is the most preferable method of the production of cell aerosol for their delivery to the lower respiratory tract.

Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut.

Effects of a New Glutamic Acid Derivative on Myocardial Contractility of Stressed Animals under Conditions of Nitric Oxide Synthesis Blockade.

Glufimet (glutamic acid derivative) in a dose of 28.7 mg/kg limited the reduction of the cardiac functional reserve in animals subjected to 24-h stress under conditions of nonselective NO synthase blockade with L-NAME (10 mg/kg). Adrenoreactivity and increased afterload tests showed that the increment of myocardial contraction/relaxation rates, left-ventricular pressure, and HR were significantly higher in glufimet-treated stressed animals with NO synthesis blockade than in animals which received no glufimet. The efficiency of glufimet was higher than that of phenibut (the reference drug).

[Cardioprotective properties of new glutamic acid derivative under stress conditions].

The effect of new glutamic acid derivative on the cardiac ino- and chronotropic functions has been studied in experiments on rats exposed to 24-hour immobilization-and-pain stress. It is established that glutamic acid derivative RGPU-238 (glufimet) at a dose of 28.7 mg/kg increases the increment of myocardial contractility and relaxation rates and left ventricular pressure in stress-tested animals by 13 1,1, 72.4, and 118.6%, respectively, as compared to the control group during the test for adrenoreactivity. Compound RGPU-238 increases the increment of the maximum intensity of myocardium functioning by 196.5 % at 30 sec of isometric workload as compared to the control group. The cardioprotective effect of compound RGPU-238 is 1.5 - 2 times higher than that of the reference drug phenibut.

Effect of GABA derivatives on the rate of thrombus formation, platelet aggregation, and plasma coagulation capacity in rats with experimental gestosis.

Experimental gestosis induced by replacement of drinking water with 1.8% NaCl promoted hypercoagulation, increased the rate and degree of platelet aggregation, and reduced clotting time in pregnant females. GABA derivatives, compounds RGPU-151, RGPU-152, and phenibut normalized parameters of hemostasis and platelet aggregation and the rate of thrombus formation in the animals. The efficiency of the test substances did not significantly differ from that of the reference drug sulodexide.

[Comparative analysis of action of beta-phenyl derivatives of glutamic and gamma-aminobutyric acid on cerebral blood flow and cerebrovascular endothelium after irreversible occlusion of the common carotid artery].

A comparative analysis of the effect of phenyl derivatives of glutamic (RGPU-135) and gamma-aminobutyric acid (Phenibut) on cerebral blood flow, vasodilatory endothelial function and the number of circulating endothelial cells desquamated in animals after irreversible occlusion of the common carotid arteries. It was found that animals treated prophylactically by RGPU-135, after occlusion of the common carotid arteries have higher cerebral blood flow and lower the severity of endothelial dysfunction than in animals treated with Phenibut.

[Effect of GABA derivative--RSMU-151 on the development of oxidative stress in rats with experimental gestosis].

Experimental gestosis induced in rats by drinking 1.8% sodium chloride solution instead of water during the entire period of pregnancy leads to activation of lipid peroxidation (LPO) process, as manifested by increased concentration of diene conjugates and malonic dialdehyde, decreased concentration of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in homogenates of rat brain, liver, uterus, and placenta. The GABA derivatives--RSMU-151 limits the damaging effect of gestosis, which is manifested by a decrease in the concentration of LPO products and by activation of the antioxidant system enzymes in all organs studied.

[Fenibut and its citrate prevent psychoneurological disorders caused by chronic stress (paradoxical sleep deprivation)].

The antistress protective action of two structural analogs of GABA, fenibut and its salt with citric acid (fenibut citrate, citrocard, RGPU-147), has been studied using a model of chronic stress caused by seven-fold 24-h deprivation of paradoxical sleep phase at an interval of 24 h between the deprivations. It is established that fenibut and fenibut citrate produce a protective action by (i) reducing the intensity of emotional disorders in the open-field test and elevated plus maze test, (ii) decreasing cognitive disorders in the tests for conditioned avoidance response and extrapolatory deliverance; and (iii) limiting stress reaction due to a decrease in the intensity of adrenal hypertrophy, thymus involution, and stomach mucous membrane ulceration. Fenibut citrate surpasses fenibut in the intensity of antistress protective action.

[Phenotropyl succinate as the means for correction of neuroimmune disturbances under conditions of informational-physical stress].

In Wistar rats, psycho-immune-modulating properties of phenotropyl succinate were studied under conditions of informational-physical stress. The effect ofphenotropyl succinate on the organism specific and unspecific resistance was studied. The data obtained indicate the phenotropyl succinate ability to release neuroimmune disturbances developing under conditions of informational-physical stress.

[Anxiosedative properties of heteryl(aryl)-containing hexahydrobenzofuranon derivatives].

The anxiosedative properties of 2-hydroxyimino-3-indolylyl(aryl)-4-oxo-2,3,4,5,6,7-hexahydrobenzofuranon derivatives have been studied using the open-field test, elevated plus-maze test, and conflict drinking procedure as developed by Vogel. It is established that all derivatives with both indole and aryl substituents produce a sedative effect. However, an anxiolytic effect is determined by the presence of indole substituent in the third position of the hexahydrobenzofuran molecule.

[Psychotropic effect of phenibut salts and their compositions with organic acids].

The spectra of psychotropic action of some phenibut salts (succunate, maleate, nicotinate) and a composition of phenibut with glutamic acid were studied. It is established, that the substances studied show psychotropic activity spectrum generally similar to that of phenibut, but different in expressiveness of some particular effects. Compound RSPU-149 exhibited the most pronounced psychotropic action: its anxiolytic effect was below, the antidepressant effect was comparable with, and the nootrope action exceeded that of phenibut.

[Gender differences in action Fenotropil and its structural analog--compound RGPU-95 on anxiety-depressive behavior animals].

Fenotropil and its structural analog--compound RGPU-95 to a greater extent reduce the severity of anxious and depressive behavior in male rats than in females. On expression of the anxiolytic compound RGPU-95 significantly exceeds Fenotropil, but inferior to Diazepam; of antidepressant activity--comparable to Melipramin and exceeds Fenotropil.

[Comparative study of immunomodulating properties of phenibut and gammoxin].

Experiments on CBA mice with model immunodepression induced by cyclophosphamide showed that phenibut (25 mg/kg) and gammoxin (25 mg/kg) recover both cellular and humoral immunoreactivity and restore lymphoproliferative processes in immunocompetent organs, which is evidence for pronounced immunocorrecting properties of these drugs. A comparative analysis of the immunomodulating activity of phenibut and gammoxin showed that the latter drug predominantly affects the process of immunocompetent cell maturation (growth in mass and cellularity of thymus and spleen--the central immunocompetent organs), while phenibut mostly influences the realization of the final reaction of the primary anti-erythrocyte immune response (significant correction of local infiltration delayed-type hypersensitivity reaction and antibody formation). This difference can be related to the fact that the drugs influence GABA receptors of different types, whereby gammoxin acts on these receptors in immunocompetent organs and phenibut acts on the receptors in lymphocytes.

Effect of citrocard on functional reserves of the heart under conditions of chronic stress.

Chronic stress exposure produces a damaging effect on the myocardium and reduces its functional (inotropic) reserves. Citrocard (50 mg/kg) and fenibut (50 mg/kg) prevent stress effects: animals receiving these preparations demonstrate higher contraction and relaxation rates and higher left-ventricular pressure during functional tests (volume load and maximum isometric load).

[Cardioprotective effect of GABA derivatives in acute alcohol intoxication].

Cardioprotective properties of GABA analogs under conditions of acute alcoholic intoxication have been studied using the following functional tests: volume loads, tests for adrenoreactivity, and maximum isometric load. The experiments showed that a 32% aqueous ethanol solution intraperitoneally injected in a dose of 8 g/kg produces a cardiotoxic action, which is manifested by a decrease in the inotropic reserve in load tests. Citrocard (50 mg/kg), phenibut (50 mg/kg), and piracetam (200 mg/kg) prevent the alcohol-induced myocardium injury, as shown by the heart contractility retained on a higher level in the test group than in the control group.

[Hygienic characteristics of working conditions and health status of workers in animal feed-processing industry]. / Gigienichaskaia kharakteristika uslovii truda i sostoianie zdorov'ia rabochikh kombikormovykh zavodov.

Studies of mixed folder processing labour conditions revealed a set of unfavourable occupational factors, including poor microclimate, high level dust discharge and bacterial contamination in the air. The major health disorders among the workers engaged therein include upper respiratory and bronchopulmonary, locomotor system and perypheral NS and skin diseases.