The review discusses modern views about the structure and functions of Epac proteins (exchange proteins directly activated by cyclic adenosine monophosphate). The involvement of Epac proteins both in the regulation of the physiological functions of the body and in the initiation of various pathological processes allows to consider them as a fundamentally new biological target for creating original, highly effective drugs. Information on existing Epac protein agonists and antagonists was collected, and the influence of Epac ligands structure on the values of their affinity and selectivity was analyzed. Presumptive mechanisms of the interaction of ligands with Epac proteins are presented.

New ortho-alkoxy analogs of the compound ALM-802 1a (N¹-(2-methoxybenzyl)-N²-[2-((2-methoxybenzyl)amino)ethyl]ethane-1,2-diamine trihydrochloride) and 1b (N¹-(2-ethoxybenzyl)-N²-[2-((2-ethoxybenzyl)amino)ethyl]ethane-1,2-diamine trihydrochloride), which differ from it by the presence of alkoxy groups in the phenyl rings only in the ortho positions. It was established that these structural changes lead to the disappearance of anti-ischemic activity. At the same time, antiarrhythmic activity was revealed in compound 1b on the models of aconitine and calcium chloride arrhythmias in rats (1 mg / kg, intravenously), which was absent in 1a.

The present work was to study the GSB-106 effect on the immobility behavior of mice Balb/c in the Porsolt test. GSB-106 was administered sub-chronically and chronically intraperitoneal in dose 1 mg/kg. GSB-106 administration significantly decreased immobility time in mice by 1.2 times after 4 days, by 1.3 times after 14 days and 1.2 times after 21 days’ injections. Thus, the dependence of the GSB-106 effect-time administration in the Porsolt test was not established.

The technique of quantitative determination of GZK-111 and CPG compounds in rat blood plasma has been developed. The analysis was carried out using the combined method of high-performance liquid chromatography with mass spectrometric detection. The method was linear in the concentration range of 25-1000 ng/ml for both compounds. Percentage of GZK-111 extraction from rat blood plasma was 57.8 %. The lower limit of detection for GZK- 111 compound was 25 ng/ml. Percentage of extraction of CPG compound was 42.5 %. The lower limit of detection of CPG compound was also 25 ng/ml.

The results of the study of chronic toxicity of the drug formulation of anxiolytic GB-115 are presented. The novel dipeptide in the form of a tablet mass was administered daily orally for 6 months to outbred rats and rabbits of the chinchilla breed at a dose of 1 mg/kg corresponding to the therapeutic and 50 mg/kg exceeding the therapeutic dose by 50 times. Clinical, laboratory and pathohistological studies performed in accordance with the General Protocol demonstrated the absence of toxic effects of the GB-115 drug formulation. The exception was the reversible changes in the coagulation activity in rats and rabbits, which were not associated with the dose of the GB-115 solid dosage from.

Homeovox, a multicomponent homeopathic treatment for laryngitis of various etiologies, was tested for allergenic properties and immunotoxicity.

Methods. 80 male albino guinea pigs and 180 male СВА, C57BL/6 and F1 hybrid (CBAхС57BL/6) mice were used in the study. In order to assess immunotoxicity, Homeovox was administrated orally to mice for 14 days at doses of 100 mg/kg and 1 000 mg/kg. To assess the allergenic properties of Homeovox, albino guinea pigs were also given the drug at doses of 100 mg/kg and 1 000 mg/kg according to the standard immunization schedules.

Results. Oral administration of Homeovox to mice for 14 days at doses of 100 mg/kg and 1 000 mg/kg did not cause significant changes in the main characteristics of immune response compared to controls. When assessing allergenicity, Homeovox at doses 100 mg/kg and 1 000 mg/kg administered according to the standard immunization schedules did not induce systemic anaphylaxis or active skin anaphylaxis in albino guinea pigs. The immunization of guinea pigs by Homeovox at the same doses in a mixture with Freund's complete adjuvant caused no delayed allergic reactions. Homeovox at a single oral dose of 1 000 mg/kg significantly decreased concanavalin A-induced inflammation in CBA mice by 58.4 %.

Conclusion. Within the dosage range investigated, Homeovox does not induce immunotoxicity, immediate- or delayed-type allergic or pseudoallergic reactions.