Effects of chronic cycloprolylglycine (CPG) and its analogues GZK-001 and GZK-002 treatment at the doses 1 and 2 mg/kg on levels of monoamines and their metabolites in BALB/c mice brain were determined by HPLC. Neurochemical data demonstrated that antidepressant-like effects of the peptides are mediated by an increase in NA and decrease in DA content in frontal cortex. Alterations in striatal monoamine metabolism were observed predominantly after CPG's analogues treatment: the concentration of DA was increased, although its rate of turnover was diminished. In hippocampus more active was CPG: the levels of NE, DA, 5-HT, and its metabolite 5-HIAA were decreased. GZK-001 (1 mg/kg) caused a decrease in the concentration of DA and 5-HIAA. The present results suggest that antidepressant-like effects of CPG and its analogues are associated with DA, NE, and 5-HT systems.

At the Zakusov Institute of Pharmacology designed and synthesized dimeric dipeptide mimetics of the 1st (GK-6) and 4th (GK-2) nerve growth factor loops, 1st (GSB-214), 2nd (GTS-201) and 4th (GSB -106, GSB-106Ac) brain-derived neurotrophic factor loops. Antidepressant activity of GSB-106 has already been established by oral and intraperitoneal administration in 0.1-5.0 mg/kg doses. Newly synthesized mimetics were studied in comparison with GSB-106 for antidepressant-like activity in the forced swim test on male Balb/c mice with a single intraperitoneal administration. It was found that only mimetic of the fourth brain-derived neurotrophic factor loop GSB-106Ac, varied from GSB-106 by replace monosuccinyl fragment to acetyl, has antidepressant activity in doses of 1.0 mg / kg and 5.0 mg / kg.

Background. Treatment of depression disorders is insufficiently effectively. It uses for increasing of treatment efficiency empirical selected combinations of antidepressants with preparations of lithium and certain others, which possess cerebroprotective aside from psychopharmacological activity. Purpose. A study the spectrums of cerebroprotective activity of derivatives of benzimidazole - diacamph and of pyrrolo-oxindole - substance R-86 and referent preparation piracetam as well as its impact on ability of antidepressants to weaken the manifestation of behavioral depression evoked by chronic inflammation.

Methods. It was investigated on slices of dorsal hippocampus in vitro by means of electrophysiological methods the impact of administrated during 10 days diacamph, substance R-86 and piracetam on evoked by deprivation of oxygen and glucose, 1 mM H₂O₂ and 50 pM N-methyl-D-aspartate damages of pyramidal neurons. It was simulates in experiments in vivo behavioral depression evoked by chronic inflammationand researched impact of diacamph, substances R-86 and piracetam on evoked by antidepressants weakening of behavioral depression main manifestations.

Results. It was ascertained, that chronic i/p administration diacamph, substance R-86 (10 mg/kg) and piracetam (100 mg/kg) rats reduced damages of hippocampal pyramidal neurons evoked by oxygen/glucose deprivation, oxidative stress and N-methyl-D-aspartate, i. e. drugs possess by cerebroprotective activity. In behavioral experiments investigate potentiating influence of diacamph and substance R-86 on affected imipramine, amitryptiline and ketamine duration of immobilization and marker of preference sucrose solution in rat behavioral depression evoked by chronic inflammation.

Conclusion. Drugs with cerebroprotective action potentiate effects of traditional and fast-acting antidepressants.

In the study of strutural and intracellular distribution of cyclo-t-prolylglycine (CPG) in brain rats in experiments on mongrel white male rats, it was found that CPG determined more in the hippocampus and cerebral cortex with predominant localization in the nuclear fraction of the rat brain, in the mitochondrial and microsomal fractions CPG is distributed approximately equivalently with a small quantitative predominance in the microsomal fraction. In an experimenlt using inbred mice of 2 lines: C57Black/6 and BALB/c, differing in behavior, opposite emotional response to stress, hypoxic influence. It was shown that the content CPG mice of the C57black/6 line are 39 % larger than in the brains of mice of the stress-unstable BALB/c line, which is probably due to differences in the manifestation of its it was shown that the content of CPG in the brain of stress-resistant mice C57Black/6 more than 39 % compared with the content of GPG in brain of mice BALB/c and the relationship between the quantitative content of CPG in the brain of these experimental animals and the manifestation of its antihypoxic effect was established.

Abstract. The study of allergenic properties and immunotoxic effects of the ready-to-use drug form of GSB-106 was carried out. The study of allergenic properties and immunotoxicity of GSB-106 was performed on male albino guinea pigs weighing 250-300 g and on male CBA, C57BL / 6, F1 hybrids (CBAxC57BL / 6) mice. When assessing immunotoxicity, GSB-106 was inject to mice per os for 14 days in doses of 2.2 mg / kg and 22 mg / kg. When studying the allergenicity, GSB-106 was injected to albino guinea pigs in doses of 1 mg / kg and 10 mg / kg according to standard regimens of immunization. The results of the study of the immunotoxicity and allergenicity of GSB-106 allow us to conclude that the injection of the ready-to-use drug form of GSB-106 in the range of studied doses does not have an immunotoxic effect and does not have allergenic properties.

Relevance. Assessment of acute toxicity is a necessary stage of preclinical research of a tablets Homeovox homeopathic. The aim of present research is study of acute toxicity Homeovox.

Methods. Homeovox was administered once orally and intraperitoneally to mice and rats in the maximum possible volumes for each of the administration methods and for each animal species, at the highest possible concentrations. Equivalent volume of 1 % starch solution was administered to animals of the control groups. Euthanasia and pathoanatomical dissection were performed 14 days after drug administration. Periods of animals intoxication with a detailed description of the observed clinical picture were registered.

Results. The median fatal doses were not identified because Homeovox did not cause death of animals at introduction of the maximum allowable volumes and maximum allowable concentrations. The morphological view of the internal organs, detected during pathoanatomical dissection of all experimental animals, did not differ from that observed in control animals.

Conclusion. It was determined that Homeovox at oral and intraperitoneal introduction concerns to practically non-toxic substances. According to classification Sidorov KK this homeopathic tablets may be related to 5th toxicity class. According to GOST 12.1.007-76 Homeovox may be related to 4th danger class.

Relevance. Assessment of chronic toxicity is a necessary stage of preclinical research a tablets Homeovox homeopathic. The aim of present research is study of chronic toxicity of a tablets Homeovox homeopathic.

Methods. Homeovox was administered orally to males and females of rats and rabbits in doses of 100 and 1 000 mg / kg for three months. The appearance and the general state of animals were observed, the dynamics of body weight, feed and water consumption, behavioral reactions, rectal temperature, state of the cardiovascular system (electrocardiography, blood pressure measurement) were evaluated, hematological, biochemical and pathomorphological examinations were conducted to determine possible toxic effects and their reversibility, possible target organs and local irritant effect.

Results. Parameters registered in the conducted studies did not get out the limits of the reference values for these species of animals. Homeovox did not cause any regular changes in the structure of the internal organs of rats and rabbits.

The study of acute and chronic toxicity of the homeopathic preparation syrup Stodal, produced by the Laboratory of Boiron, France, widely used in medical practice as an effective antitussive agent. Stodal with a single intragastric administration to outbred mice and rats at doses of 5, 10, 15, 20 and 25 ml / kg and intraperitoneal administration to rats at doses of 2.5; 5; 7.5; 10 and 12.5 ml / kg did not cause death of animals. In experiments on mice in females with intraperitoneal administration of homeopathic syrup Stodal LD₅₀ was 17.2 (13.1 - 22.6) ml/kg and in males LD₅₀ was 19.6 (16.1 - 24.0) ml/kg. Homeopathic syrup Stodal with daily oral administration to rats and rabbits in doses of 1 ml / kg and 10 ml/kg for one month did not cause changes in the General condition, behavior, appearance and pronounced changes in body weight of animals. Toxic effects of stodal syrup were not observed in clinical and laboratory, pathomorphological and histological studies performed in the conventional volume.