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The Department of Pharmacology of the Institute of Experimental Medicine was established in the autumn of 1923 on the initiative of the institutes leadership. Professor Nikolai Pavlovich Kravkov (18651924), the most respected domestic pharmacologist at that time and the head of the Department of Pharmacology of the Military Medical Academy, was invited as the alleged head of the department. However, N.P. Kravkovs untimely death in April 1924 precluded the department from developing extensive research in Pharmacology. Professor Vladimir Vasilyevich Savich (18741936), a student of I.P. Pavlov who focused his main research on the effect of medicinal substances on the nervous regulation of the cardiovascular system, gastrointestinal tract, endocrine system, and water metabolism, led the department from 1924 to 1936. The mechanism of the direct impact of drugs and poisons on organs and tissues was studied using both isolated organs, notably endocrine glands, and classical conditioned reflex techniques. In 1936, the department was disbanded in connection with the death of the head (V.V. Savich) and the reorganization of the institutes structure. Professor S.V. Anichkov (18921981), who later became the Hero of Socialist Labor, laureate of the Lenin and State Prizes of the USSR, and academician of the USSR Academy of Medical Sciences, revived the department in 1948 and remained its permanent head until his death (in July 1981). Along with him were well-known researchers Professors V.M. Karasik, N.V. Khromov-Borisov, I.S. Zavodskaya (who led the department from 1981 to 1984), Y.S. Borodkin (who led the department from 1984 to 1992), N.A. Kharauzov, V.E. Ryzhenkov, N.S. Sapronov (who led the department from 1992 to 2011), P.P. Denisenko, and N.A. Losev. The main focus of the department from 1948 to 1984 was the integration of fundamental pharmacological advancements with the introduction of drugs into healthcare practice. Currently, the Department of Neuropharmacology. S.V. Anichkova is one of the largest research centers in Russia, focusing on fundamental research in Pharmacology. Professor P.D. Shabanov has been the head of the department since 2011. The department divided into four laboratories: the Laboratory of Chemistry and Pharmacology of Medicinal Products (led by Doctor of Medical Sciences, E.R. Bychkov), the Laboratory of General Pharmacology (led by Doctor of Biological Sciences, Prof. A.A. Lebedev), the Laboratory of Biochemical Pharmacology (led by Doctor of Medical Sciences, Prof. P.D. Shabanov), and the Laboratory of Synthesis and Nanotechnology of Medicinal Substances (led by Doctor of Biological Sciences, Prof. L.B. Piotrovsky).
The Department of Pharmacology of the Institute of Experimental Medicine was established in the autumn of 1923 on the initiative of the institutes leadership. Professor Nikolai Pavlovich Kravkov (18651924), the most respected domestic pharmacologist at that time and the head of the Department of Pharmacology of the Military Medical Academy, was invited as the alleged head of the department. However, N.P. Kravkovs untimely death in April 1924 precluded the department from developing extensive research in Pharmacology. Professor Vladimir Vasilyevich Savich (18741936), a student of I.P. Pavlov who focused his main research on the effect of medicinal substances on the nervous regulation of the cardiovascular system, gastrointestinal tract, endocrine system, and water metabolism, led the department from 1924 to 1936. The mechanism of the direct impact of drugs and poisons on organs and tissues was studied using both isolated organs, notably endocrine glands, and classical conditioned reflex techniques. In 1936, the department was disbanded in connection with the death of the head (V.V. Savich) and the reorganization of the institutes structure. Professor S.V. Anichkov (18921981), who later became the Hero of Socialist Labor, laureate of the Lenin and State Prizes of the USSR, and academician of the USSR Academy of Medical Sciences, revived the department in 1948 and remained its permanent head until his death (in July 1981). Along with him were well-known researchers Professors V.M. Karasik, N.V. Khromov-Borisov, I.S. Zavodskaya (who led the department from 1981 to 1984), Y.S. Borodkin (who led the department from 1984 to 1992), N.A. Kharauzov, V.E. Ryzhenkov, N.S. Sapronov (who led the department from 1992 to 2011), P.P. Denisenko, and N.A. Losev. The main focus of the department from 1948 to 1984 was the integration of fundamental pharmacological advancements with the introduction of drugs into healthcare practice. Currently, the Department of Neuropharmacology. S.V. Anichkova is one of the largest research centers in Russia, focusing on fundamental research in Pharmacology. Professor P.D. Shabanov has been the head of the department since 2011. The department divided into four laboratories: the Laboratory of Chemistry and Pharmacology of Medicinal Products (led by Doctor of Medical Sciences, E.R. Bychkov), the Laboratory of General Pharmacology (led by Doctor of Biological Sciences, Prof. A.A. Lebedev), the Laboratory of Biochemical Pharmacology (led by Doctor of Medical Sciences, Prof. P.D. Shabanov), and the Laboratory of Synthesis and Nanotechnology of Medicinal Substances (led by Doctor of Biological Sciences, Prof. L.B. Piotrovsky).
BACKGROUND: Until now, the neurotropic effect, in particular the effect on the emotional behavior of oxy-coumarins, has not been adequately studied. There are only few data on their central action. Currently, research is underway on the synthesis of new compounds based on natural oxy-coumarins, which will potentially have a higher biological activity. AIM: Was to study the central action of new oxycoumarin-based compounds IEM-2886, LVM-99, LVM-S144, in particular, on compulsive behavior in rats. MATERIALS AND METHODS: To assess the behavior of Wistar rats, the Marble-test and Elevated plus maze methods were used. Oxycoumarin derivatives (IEM-2886, LVM-99, LVM-S144) were injected intraperitoneally at doses of 1, 10 and 25 mg/kg. The effectiveness of the drugs was judged by the number of balls buried in the Marble test and by the duration of staying in the open and closed sleeves of the Elevated plus maze. Results. It was shown that in the Marble test, oxycoumarin-based compounds (IEM-2886, LVM-99, LVM-S144) caused a decrease in the number of buried balls, which shows their anti-compulsive effect. After administration of IEM-2886, LVM-99, LVM-S144 (125 mg / kg) compounds, dose-dependent effects were observed (p 0.05). The elevated plus maze test did not show the anxiolytic effect typical for tranquilizers. Moreover, after the administration of IEM-2886 and LVM-S144 at a dose of 25 mg / kg, an increase in the time spent in the closed sleeve of the maze (p 0.05) was observed, i.e. an anxiogenic effect. CONCLUSION: Thus, oxy-coumarin-based compounds are selective for the assessment of anticompulsive effects.
BACKGROUND: Coumarins are naturally occurring molecules with a wide range of pharmacological activities. Their use is limited by difficulties in isolation from plant material, toxicity, and low solubility. The chemical structure of these compounds makes coumarins promising for the synthesis of a large number of derivatives that may have biological activity and be of interest as potential drugs. We had synthesized coumarin derivatives, two of which IEM-2266 (7-alkoxycoumarin derivative) and IEM-2267 (4-aminocoumarin derivative) have shown antihypoxic effect in mice in models of hypoxic hypoxia with hypercapnia, histotoxic and hemic hypoxia. AIM: The aim of this work was to study the antihypoxic effect of new coumarin derivatives IEM-2266 and IEM-2267 under conditions of acute hypobaric hypoxia in rats. METHODS: The experimental work was performed on male Wistar rats weighing 200220 g. Acute hypobaric hypoxia was induced in rats by placing them in a flow pressure chamber. Compounds IEM-2266 and IEM-2267 were administered intraperitoneally at the dose 25 mg/kg once 50 minutes before hypoxia. Mexidol at the dose of 100 mg/kg was used as a reference drug. The antihypoxic activity of the substances was assessed according to the following indicators: 1) lifespan at the critical height 11,000 m; 2) the value of the individual high-altitude threshold; 3) individual resistance to hypoxia calculated from high-altitude threshold, expressed in points; 4) survival at consistently presented heights; 5) determination of the structure of population resistance according to the ratio of animals with low, medium and high resistance to hypoxia. RESULTS: New coumarin derivatives IEM-2266 and IEM-2267 exhibited antihypoxic activity under acute hypobaric hypoxia conditions. With the use of IEM-2266, IEM-2267, and Mexidol, the lifespan of animals at a critical altitude of 11,000 m increased by 2.4, 5.4, and 4.9 times, respectively, compared with the control, the point based assessment of individual resistance to hypoxia increased by 36, 66 and 67%, the absolute value of high-altitude threshold increased significantly (p 0.05). Coumarin derivatives changed the structure of population resistance, increasing the proportion of highly resistant animals. CONCLUSIONS: Thus, the effect of IEM-2267 is comparable, and even exceeds the effect of Mexidol. The 7-alkoxycoumarin derivative IEM-2266 has a moderate, and the 4-aminocoumarin derivative IEM-2267 has high antihypoxic activity in rat AHbH conditions.
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