The investigation purpose. N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (ALM-802 compounds) cardioprotective effect has been studied in rat models of subendocardial ischemia caused by isoproterenol and dobutamine. Material and methods. Acute subendocardial myocardial ischemia in anesthetized rats (urethane 1300 mg/kg, i.p.) was caused by infusion of isoproterenol (20 µg/kg/min i.v.) or dobutamine (80 µg/kg/min i.v.). Results. It was shown that in anesthetized rats, isoproterenol and dobutamine caused almost the same ST-segment depression in the II standard ECG lead. The compound ALM-802 (2 mg/kg i.v.), administered 2 minutes before the infusion start of isoproterenol or dobutamine, equally prevented the occurrence of ischemic changes on the ECG. Conclusion. The non-selective beta-adrenomimetic isoproterenol and the selective β1-adrenomimetic dobutamine cause subendocardial ischemia of the same intensity in anesthetized rats. The compound ALM-802 has a pronounced anti-ischemic effect on both models.
28 April 2020 in Pharmacokinetics and Pharmacodynamics
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.
19 July 2023 in Pharmacokinetics and Pharmacodynamics
The antiarrhythmic activity of bis-alkoxyphenyltriazaalkanes 1 and bis-alkoxyphenyldiazaalkanes 2 was analyzed in a model of reperfusion arrhythmia in rats. It was found that the key requirements for the compounds activity in this model are the use of 2,3,4 trimethoxyphenyl aromatic pharmacophores and the presence of a central nitrogen atom in the linker. The most active compounds were ALM-802 (trihydrochloride N1–(2,3,4-trimethoxybenzyl)-N2– {2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine) and ALM-811 (N1-(2,3,4-trimethoxybenzyl)-N3-{3-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,3-propanediamine trihydrochloride), which significantly prevented the development of ventricular tachycardias and/or ventricular fibrillation.
20 October 2021 in Russian Journal of Occupational Health and Industrial Ecology
Tritium is one of the most important dose-forming radionuclides that determine the radiation situation in the area where nuclear fuel cycle enterprises are located. At the same time, it is not possible to catch the tritium formed during the operation of a nuclear power plant using modern, efficient and cheap technologies. This causes an increase in its concentration in environmental objects and an increase in the contribution of technogenic tritium to the radiation load of the population. Therefore, the task of monitoring the formation of tritium during the operation of nuclear power plants, the content of tritium in emissions and discharges of nuclear power plants, as well as the distribution of this radionuclide in the environment is especially urgent today. The study aims to analyze the environmental pollution due to emissions and discharges of tritium from the Kalininskaya nuclear power plant, the process of spreading tritium by air, as well as the accumulation of this radionuclide in water bodies, soil and food products grown in the area of the nuclear power plant. The following methods, developed by the specialists of the Burnasyan Federal Medical Biophysical Center were used during the research: 1) "Method for determining the volumetric activity of organic and inorganic tritium compounds in water bodies by liquid scintillation spectrometry". 2) "Methodology for determining the concentration of organic and inorganic tritium compounds in the air of the environment and industrial premises". 3) "The method for determining the specific activity of tritium compounds in soil and vegetation" was developed and tested in the course of field studies at the Kalinin NPP. As a sample preparation we used the method based on burning a selected sample in a specialized Pyrolyser-6 Trio oven. All prepared counting samples were measured by liquid scintillation spectrometry on a counter Tri-Carb 3180TR/SL. On the basis of an integrated approach to assessing the content of tritium and its compounds in air, water, soil and food, an analysis of the formation of environmental pollution due to emissions and discharges of tritium from the Kalinin NPP was carried out. It is shown that the transport of emissions from the NPP by air and the wind direction prevailing in the territory of the NPP location have a significant importance in the formation of the contribution to the ingress of tritium into foodstuffs. The necessity of taking into account the ingress of tritium and its compounds with nuclear plant emissions into the environment in the task of optimization of radiation protection of the population under conditions of normal operation of NPP is shown.
1 January 2020 in Problems of Biological, Medical and Pharmaceutical Chemistry