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Biography. Oswald Schmiedeberg (1838-1921) was a son of a bailiff and a maid of honour, the eldest of the six children in the family. He was born and educated in the Russian Empire. Scientific activity. All his life he was completely devoted to science, making experimental pharmacology an independent scientific discipline, and was able to bring it to the international level. O. Schmiedeberg studied the action of muscarine and nicotine, digitoxin, hypnotics and analeptics. He was the first to introduce the concept of “pharmacodynamics” and “pharmacokinetics” of a drug. With his participation, the world’s first pharmacological journal was founded, which is still published today. Science school. Working for many years at the University of Strasbourg, Schmiedeberg managed to educate about 120 students – professors from 20 countries of the world, many of whom later founded experimental pharmacology in their countries, for example, Abel in the USA, and N.P. Kravkov in Russia. Scientific activity of Schmiedeberg influenced scholars of his time and for generations to come, creating the preconditions for new high-profile discoveries and even for receiving Nobel prizes. But Oswald Schmiedeberg failed to obtain this high award himself, though he had been nominated 14 times.

In experiments on the isolated rat heart there were studied the effects of different doses (21.43 mg/kg/day and 85.72 mg/kg/day) 2-ethyl-6-methyl-3 hydroxypyridine succinate ("EkoPharmInvest", Russia), on the contractile function of isolated hearts subjected to prior doxorubicin model (20 mg/kg, intraperitoneal) of pathology. The dynamic of the power mechanisms of ion transport was evaluated by imposing high heart rate (480 BPM) and increase concentration of Са2+ to 5 mmol in perfusate. The results indicate that Mexicor at the dose of 21.43 mg/kg/day does not provide a cardioprotective effect in this model of pathology. Mexicor has the cardioprotective effect at the dose of 85.72 mg/kg/day in relation to the isolated heart, that is resulted in the recovery of the contractile function of the heart and reducing the "diastole defect" (SТТI).

Parkinson's disease is the most common neurodegenerative disorder after Alzheimer's disease. The aim of this study was to investigate the pharmacokinetic parameters of the mGluR4 receptor blocker Rapitalam on rabbits. There was developed the method of the quantitative determination of Rapitalam in the blood plasma of rabbits using high performance liquid chromatography with tandem mass spectrometric detection. The study was performed on 12 rabbits (males, weighing between 3,300 to 3,500 g). In intragastric dosing of the substance was administered using a gastric tube in the form of suspension in water 0.9 mg/ml, 9 mg/ml, and 90 mg/ml at a dose of 0.3 mg/kg, 3 mg/kg and 30 mg/kg. After the administration of the substance blood was sampled through a catheter in a volume of 0.5 ml in polypropylene tubes containing 20 µl of 5% EDTA before and 10, 15, 30, 60, 120, 240, 480, 1440 minutes after administration. The mean absorption time (MAT) of Rapitalam was 268.1 minutes or 4.5 hours. The half-life is longtime and it was 176.4 minutes (2.9 hours) for intravenous and 362.2 minutes (6.0 hours) for intragastric administration. The absolute bioavailability of the intragastric dosing was 26.8%. The main pharmacokinetic parameters of the substance was established on rabbits that allow you to optimize the future use of it's as a potential drug for the treatment of Parkinson's disease.

For the first time in vitro experiments there were studied the inhibitory activity and safety of potential molecules arginase II selective inhibitors from the group of norleucine derivatives. Also first the substance under the code ZB49-0010C from the group of norleucine derivatives showed the greatest selectivity and inhibitory activity against arginase II in experiments in vitro. However, this substance in vivo exerts dose-dependent hypotensive action and cardioprotective and endothelial protective effects on the L-NAME induced and homocysteine-induced endothelial dysfunction (ED), which are most pronounced at a dose of 10 mg/kg in intragastric administration. Endothelial protective effect consists of in preventing the increase of coefficient of endothelial dysfunction (CED) and the decrease in the concentration of stable metabolites of nitric oxide in the blood plasma. Cardioprotective effect consists of in preventing the increase of the level of left ventricular pressure during the test for adrenoreactivity and reducing of the cardiac reserve during the overload resistance test, and also in preventing the development of the left ventricular hypertrophy. As part of the study there was investigated the dose-dependent anti-ischemic effect of the arginase II selective inhibitor, substance ZB49-0010C on the chronic limb ischemia in rats, which most pronounced at a dose of 10 mg/kg and consists of in preventing the fall in microcirculatory level on the 29th day of the experiment in the ischemic limb and a protective effect based on the morphological examination of the muscle tissue.

Recent studies confirm the need to find means to correct ischemic / reperfusion injury due to the hemodynamic medicine, which are already known do not have the proper cardioprotective effects. Key issue is the possibility of drug effects on the mitochondria of cardiomyocytes that controls the aerobic metabolism and maintenance of ATP admission into cardiomyocytes. Moreover mitochondria are the target of ischemia / reperfusion injury and involved in the cardioprotective mechanism ischemia and pharmacologic pre- and postconditioning. Effect of nitric oxide during ischemic reperfusion directed to mitochondria, is considered as the ultimate goal of cardioprotection. Preconditioning effects is begun from sarcolemmal membrane and then is directed to the cytoplasm through a plurality of stages of enzymes, including nitric oxide synthase (NOS), soluble guanylatecyclase (sGC) and protein kinase G (PKG). Thus, the signal is transmitted to the mitochondria, where it occurs cardioprotection. It is proved that the mitochondria provides protection of the heart against ischemia-reperfusion injury by opening the mitochondrial ATP-sensitive K + channels and by converting the capacity of mitochondria. Metabolic modulation concept can be used in the development of strategies cardioprotection for treatment in ischemic / reperfusion myocardial injury.

A method of quantitative determination of SS-68 derivative of indole in rabbit blood plasma by high performance liquid chromatography with tandem mass spectrometric detector (HPLCMS/MS). Conducted pharmacokinetic studies SS-68 in the body of rabbits. Set the main pharmacokinetic parameters of the substance that allow you to optimize the future use of it’s as a potential drug in cardiology practice.

Purulent meningitis (PM) is a severe disease, characterized by high mortality and a formation of a residual neurological deficit. Loss of treatment of PM leads to the lethal outcome in 100% of cases. In addition, death and the development of residual neurological complications are possible despite adequate therapy. The aim of the study was to evaluate the cerebroprotective effects of a new pharmacological compound 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid (EMHDPA) on the bacterial purulent meningitis in a model of experimental pneumococcal meningitis. Meningitis was simulated by intrathecal injection of the suspension containing Streptococcus pneumoniae at the concentration of 5 × 109 CFU/mL. The cerebroprotective effect was evaluated by survival rates, the severity of neurological deficit, investigatory behaviors, and results of short-term and long-term memory tests. The group administered with EMHDPA showed high survival rates, 80%. Animals treated with the studied compound showed a higher clinical assessment of the rat health status and specific force, and a lesser intensity of neurological deficit compared to the control group (p < 0.05). Locomotor activity of the animals treated with EMHDPA was significantly higher compared to the control group (p < 0.05). There is a decrease in the activity of all estimated indicators of oxidative stress in the group administered with 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid relative to the control group: a decrease in the activity of catalase—17%, superoxide dismutase—34%, malondialdehyde and acetylhydroperoxides—50%, and nitric oxide—85% (p < 0.05). Analysis of the data obtained during the experiment leads to the conclusion about the effectiveness of 2-ethyl-6-methyl-3-hydroxypyridine-2,6-dichlorophenyl(amino)phenylethanoic acid in the treatment of the experimental PM.

The endotelio- and cardioprotective effects of vitamin B6 (2 mg/kg) and folic acid (0.2 mg/kg) upon modeling of methionine-induced hyperhomocysteinemia via methionine intragastric administration at a dose of 3 g/kg were studied. It was shown that the combined use of vitamin B6 and folic acid allows on the background of a significant reduction in homocysteine concentrations normalizing the endothelial dysfunction coefficient and the parameters of maximum left ventricular pressure in response to intravenous administration of adrenaline. The research was partially supported by the grant of the President of the Russian Federation №MD-4711.2015.7.

For the first time a complex of L-arginine sodium salt of sulfate of cellulose acetate on activated carbon. To investigate the processes of sorption-desorption of L-arginine in a model environment. In animal experiments it was shown that granulirovannye the form of a combined preparation in dosages of 30 mg/kg, 70 mg/kg and 200 mg/kg exhibits a pronounced anti-hypertensive, endothelioprotecive and cardioprotective activity in a dosage of 200 mg/kg.

A model test-system was developed for validation in vitro of antihypoxic and endothelio-differentiating activity of newly created glycogen synthase kinase-3 inhibitors in comparison with the reference drug β4-thymosin.

We developed a method of quantification of the new antidiabetic drug 3-(1h-benzimidazole-2-yl)-1,2,2-trimethyl-cyclopentane-carbonic acid (c7070) in the blood plasma of rats by high-performance liquid chromatography with mass-spectrometric detection. The analytical range of the method was 0.02-3876.0 μg in 1 ml of blood plasma. The research was partially supported by the grant of the President of the Russian Federation № MD-4711.2015.7 and МК-6135.2016.4.

We investigate influence of human recombinant erythropoietin different dosage on blood flow velocity and morphological changes in liver during ischemic and reperfusion injury. It was proved what optimal preconditioning dosage is 50 IU/kg.

The experiment was carried out in female white Wistar rats. The effects of recombinant erythropoietin, rosuvastatin and their combination were investigated based on the blood supply to the bone after a modelled experimental osteoporosis. It was found that the studied drugs prevent decrease of bone microcirculation in cases of osteoporosis and in callus tissue in experimental osteoporotic fractures, positively influencing the course of reparative regeneration of bone tissue.

An important task of pharmacology is to find effective agents to improve retinal microcirculation and resistance to ischemia. The purpose of the study is to pharmacologically evaluate the retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate in a rat model of retinal ischemia−reperfusion. A retinal ischemia−reperfusion model was used, in which an increase in intraocular pressure (IOP) to 110 mmHg was carried out within 30 min. The retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate at a dose of 3.8 mg/kg, in comparison with nicotinic acid at a dose of 2 mg/kg and emoxipine at a dose of 2 mg/kg, was estimated by the changes in the eye fundus during ophthalmoscopy, the retinal microcirculation level with laser Doppler flowmetry (LDF), and electroretinography (ERG) after 72 h of reperfusion. The use of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate prevented the development of ischemic injuries in the fundus and led to an increase in the retinal microcirculation level to 747 (median) (lower and upper quartiles: 693;760) perfusion units (p = 0.0002) in comparison with the group that underwent no treatment. In the group with the studied substance, the b-wave amplitude increased significantly (p = 0.0022), and the b/a coefficient increased reliably (p = 0.0002) in comparison with the group with no treatment. Thus, 2-ethyl-3-hydroxy-6-methylpyridine nicotinate has established itself as a potential retinoprotector.

Currently, there is no doubt surrounding a theory that the cardiotropic effects of sex hormones can be due to their direct effect on the cardiovascular system. In recent years, interest in the study of steroid glycosides has increased. We studied the effects of furostanol glycosides (protodioscin and deltozid) from the cell culture of the Dioscorea deltoidea (laboratory code DM-05) on the physiological and biochemical parameters of vascular endothelial function in hypoestrogen-induced endothelial dysfunction after bilateral ovariectomy. It was shown that the use of DM-05 at a dose of 1 mg/kg makes it possible to prevent the development of arterial hypertension (the level of systolic blood pressure (SBP) decreases by 9.7% (p < 0.05) and diastolic blood pressure (DBP) by 8.2%), to achieve a decrease in the coefficient of endothelial dysfunction by 1.75 times against the background of a hypoestrogenic state. With DM-05, an increase in the concentration of stable nitric oxide metabolites (NOx) by 45.6% (p < 0.05) and an increase in mRNA endothelial nitric oxide synthase (eNOS) expression by 34.8% (p < 0.05) was established, which indicates a positive effect of furostanol glycosides on the metabolism of nitric oxide after ovariectomy. Positive dynamics in the histological structure of the heart and the abdominal aorta indicate the pronounced endothelio- and atheroprotective effects of DM-05.

An important task of pharmacology and ophtalmology is to find specific and highly effective agents for correcting retinal ischemia. The objective of this study is to increase the effectiveness of pharmacological correction of retinal ischemia by using new 3-hydroxypyridine derivative⁻l-isomer of ethylmethylhydroxypyridine malate. A modification to the retinal ischemia-reperfusion model was used, in which an increase in intraocular pressure is carried out by mechanical pressure (110 mmHg) to the front chamber of the eye for 30 min. The protective effects of l-isomer of ethylmethylhydroxypyridine malate in comparison with Emoxipine as pretreatment, with parabulbar injection, based on the model of retinal ischemia-reperfusion, were estimated by the changes in the ratio of the amplitudes of the a- and b-waves of electroretinography (the b/a coefficient) and ophthalmoscopy. The use of l-isomer of ethylmethylhydroxypyridine malate improves the retinal electrophysiological state after 72 h of reperfusion; in the group of rats treated with l-isomer of ethylmethylhydroxypyridine malate, the coefficient b/a was reliably increased by 9.5%, p < 0.05, in comparison with animals treated with Emoxipine, and by 91.7%, p < 0.05, in comparison with the group with no treatment. Furthermore, it prevents the development of ischemic changes in the retina observed in ophthalmoscopy to a greater extent than Emoxipine.