Influence of Particle Size on the Anticonvulsant Activity of Propoxazepam

The granulometric composition of new analgesic substance (7-bromo-5-(o-chlorophenyl)-3-propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one) was characterized by methods of crystals microscopy and lazer diffraction,. The single polymorphic phase demonstrated by differential scanning calorimetry, X-ray diffraction analysis, Raman and IR-spectroscopy. On the base of the anticonvulsive effect on mice in compare to coarse сcrystalline sample the conclusion about the higher pharmacological effect for the disperse sample had been demonstrated

Subunit-dependent interaction of propoxazepam and its metabolite with the -aminobuturic acid type A receptor

Benzodiazepines (BDZ) are widely used in clinics in the treatment of psychiatric disorders, and their main action is considered to be determined by more selective binding with α1, α2, α3 or α5 subunits of GABA receptor. The aim of this work was studying of the molecular mechanism of action of new analgesic – propoxazepam and its metabolite (3-hydroxypropoxazepam) on α1, α2, α3, α4 or α5 subunits containing GABAA channels. Materials and methods GABA ha1b3g2, ha2b3g2, ha3b3g2, ha4b3g2 and ha5b3g2 ionotropic GABAARs expressed in HEK293 were used on the automated SP384PE Patch Clamp system. In addition, Propoxazepam, 3-hydroxypropoxazepam, diazepam (positive allosteric modulator) and GABA (positive control) were administered at concentrations 0.001–300 nM to determine the EC50 and Emax for corresponding substances. Results The α subunit plays a significantl role in determining the receptor’s affinity for propoxazepam and 3-hydroxypropoxazepam. The rank order of decreasing EC50 are α1 = α5> α2 > α3 > α4 (propoxazepam) and α1> α2> α5 > α3 > α4 (3-hydroxypropoxazepam), and for Emax α3 > α2 >α5 > α1 > α4 (propoxazepam), α3 > α1 > α2> α5 > α4 (3-hydroxypropoxazepam). The data, transformed to Emax/EC50, show that propoxazepam exhibits tenfold (compared to diazepam) activity (taking into account the magnitude of the maximum effect) to the α3 subunit, which distinguishes it from 3-hydroxypropoxazepam. Conclusion Due to the determined selectivity of propoxazepam for binding with different α subunit-containing GABAA-receptors (mostly α3 and α2 types), it has the potential to provide analgesia with less sedation than non-selective BDZ

Biological Earth observation with animal sensors

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change

Findings of new phytoplankton species in the Barents Sea as a consequence of global climate changes

Over the past few decades, the Earth’s climate has been characterized by a stable increase in temperature, which in many regions leads to a change in the composition of flora and fauna. A striking manifestation of this process is the appearance in ecological communities of new, uncharacteristic for them, species of animals and plants. One of the most productive and at the same time the most vulnerable in this respect are the marine ecosystems of the Arctic. This article is devoted to the analysis of findings of vagrant phytoplankton species in the Barents Sea, a body of water experiencing especially rapid warming due to an increase in the volume and temperature of incoming Atlantic water. For the first time, fundamental questions are considered: how widely these species are distributed over the Barents Sea area, and in what seasons do they reach high levels of abundance. The material for the present work was planktonic collections made during expedition surveys of 2007–2019 in different seasons throughout the Barents Sea. The water samples were taken using a rosette Niskin bottle sampler. The plankton net with a 29 µm mesh size was applied for filtering. The obtained material was processed according to standard hydrobiological methods and followed by subsequent microscopy for taxonomic identification of organisms and cell counting. The results of our observations show that vagrant microplankton species do not create a stable population that persists throughout the annual development cycle. Their major presence is noted in the autumn-winter period, the smallest in the summer. The distribution of invaders is strictly tied to warm jets of currents, while the weakening of the inflow of Atlantic water masses deep into the Barents Sea from the west is a limiting factor for their penetration into its eastern part. The southwestern and western parts of the basin are characterized by the most significant number of floristic finds; from here, towards the north and east, their number decreases. It can be concluded that at present the proportion of vagrant species in the Barents Sea, both in species diversity and in the total biomass of the algocenosis, is insignificant. They do not change the structure of the community as a whole, and their presence does not have any negative impact on the ecosystem of the Barents Sea pelagic. However, at this stage of research, it is too early to predict the environmental consequences of the phenomenon under study. Given the growing number of recorded cases of finds of species uncharacteristic for the Arctic, there is a possibility that this process may disrupt the biological stability of the ecosystem and even lead to its destabilization

Фізіологічні аспекти поведінкової активності щурів, їх тривожності і пам’яті в умовах введення повного агоніста гамка-рецепторного комплексу пропоксазепама

The action of 7-bromo-5 (o-chlorophenyl) -3-propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) with prolonged administration in various doses on behavioural reactions, anxiety and the memory of rats, as well as their muscle tone was estimated, which is important paying attention to its main (anticonvulsant and analgesic) pharmacological effects.The aim of the study was a comparative assessment of the severity and duration of propoxazepam effect after its administration to rats at doses of 2, 5 and 10 mg/kg (10 days) on higher functions of the central nervous system according to indicators such as motor and exploratory activity, as well as reference and working memory .Materials and methods. The study was conducted on 40 Wistar rats weighing 220-290 g. The psychophysiological state of the animals was evaluated using the "open field" test, the formation of spatial working and long-term memory in a radial eight-arm maze, muscle relaxation, imbalance and movements coordination - using the "rotating rod" method. Statistical processing was performed in Microsoft Excel 2016 with AtteStat 12.The results of the study. When comparing the test results of the "open field", "radial labyrinth" and "rotarod" in groups of animals that were administered different doses of the compound, it was found that, in general, these parameters at doses of 2 mg/kg and 5 mg/kg statistically significantly different (increase) from control values, but are similar. At a dose of 10 mg/kg, most of the parameters (except for the rotarod test) for these animals were characterized by a downward trend.Conclusions. The administration of the drug in doses of 2, 5 and 10 mg/kg leads to a decrease in anxious behaviour of animals, which is also accompanied by a pronounced dose-dependent negative effect on the endurance, coordination and memory of animals. The administration of the drug at a dose of 10 mg/kg impaired the learning ability of animals and reduced memory function. This should be considered in clinical studies of the compoundУстановлено действие 7-бром-5(о-хлорфенил)-3-пропокси-1,2-дигидро-3Н-1,4-бенздиазепин-2-она (пропоксазепама) при его длительном введении в разных дозах на поведенческие реакции, тревожность и память крыс, а также на их мышечный тонус, что является важным с учетом его главных (противосудорожный и анальгетический) фармакологических эффектов.Целью исследования была сравнительная оценка выраженности и длительности влияния пропоксазепама при его введении крысам в дозах 2, 5 и 10 мг/кг (10 дней) на высшие функции центральной нервной системы по таким показателям, как двигательная и поисковая активность, а также референтная и рабочая память.Материалы и методы. Исследование проведено на 40 крысах линии Вистар массой 220-290 г. Психофизиологическое состояние животных оценивали методом «открытого поля», формирование пространственной рабочей и длительной памяти в радиальном восьмирукавном лабиринте, мышечную релаксацию, нарушение равновесия и координации движений - методом «вращающегося стержня». Статистическая обработка осуществлялась в Microsoft Excel 2016 с пакетом AtteStat 12.Результаты исследования. При сравнении показателей тестов «открытое поле», «радиальный лабиринт» и «ротарод» у групп животных, которым вводились разные дозы соединения, было установлено, что в целом, указанные параметры при дозах 2 мг/кг и 5 мг/кг статистически достоверно отличаются (повышаются) от контроля, но одинаковы между собой. В дозе 10 мг/кг большинство параметров (кроме ротарод-теста) для этих животных характерной была тенденция к снижению.Выводы. Введение препарата в дозах 2, 5 и 10 мг/кг приводит к снижению тревожного поведения животных, что также сопровождается выраженным дозозависимым негативным влиянием на выносливость, координацию и память животных. Введение препарата в дозе 10 мг/кг ухудшало способность животных к обучению и снижало память. Указанное необходимо учитывать при клинических исследованиях соединенияВстановлено дію 7-бром-5 (о- хлорфеніл) -3-пропокси-1,2-дигідро-3Н-1,4-бенздіазепін-2-ону (пропоксазепаму) при його тривалому введені у різних дозах справляє виражений вплив на поведінкові реакції, тривожність і пам’ять щурів, а також на їх м’язовий тонус, що важливо з огляду на головні (протисудомний та аналгетичний) фармакологічні ефекти цієї речовини.Метою дослідження була порівняльна оцінка виразності та тривалості впливу на вищі психічні функції та функції підтримання м’язового тонусу і координацію рухів центральної нервової системи щурів уведення впродовж10 діб пропоксазепаму у дозах 2; 5 та 10 мг/кг).Матеріали та методи. Дослідження проведено на 40 щурах лінії Wistar масою 220-290 г. Психофізіологічний стан тварин оцінювали методом “відкритого поля”, формування просторової робочої і довготривалої пам'яті у радіальному восьмирукавному лабіринті, м'язову релаксацію, порушення рівноваги і координації рухів - методом обертового стрижня. Статистична обробка виконувалася у Microsoft Excel 2016 з пакетом AtteStat 12.Результати дослідження. При порівнянні показників тестів «відкрите поле», «радіальний лабірінт» та «ротород» у груп тварин, яким вводилися різні дози сполуки було виявлено, що в цілому, зазначені параметри при дозах 2 мг/кг та 5 мг/кг достовірно підвищуються стосовно тварин контрольної групи, але не відрізняються залежно від величини цих доз. Щодо дози 10 мг/кг, то у більшості випадків (окрім ротород-тесту) її введення дещо знижувало досліджувані показники.Висновки. Введення препарату в дозах 2, 5 та 10 мг/кг призводить до зниження тривожної поведінки тварини, що також супроводжується вираженим дозозалежним негативним впливом на витривалість, координацію і пам'ять тварин. Введення препарату в дозі 10 мг/кг погіршувало здатність тварин до навчання і знижувало пам'ять, Зазначене необхідно враховувати при клінічних дослідженнях сполук

Physiological Aspects of Rat Activity, Their Anxiety and Memory After Administration of Full Gabaa-receptor Complex Agonist Propoxazepam

The action of 7-bromo-5 (o-chlorophenyl) -3-propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) with prolonged administration in various doses on behavioural reactions, anxiety and the memory of rats, as well as their muscle tone was estimated, which is important paying attention to its main (anticonvulsant and analgesic) pharmacological effects.The aim of the study was a comparative assessment of the severity and duration of propoxazepam effect after its administration to rats at doses of 2, 5 and 10 mg/kg (10 days) on higher functions of the central nervous system according to indicators such as motor and exploratory activity, as well as reference and working memory .Materials and methods. The study was conducted on 40 Wistar rats weighing 220-290 g. The psychophysiological state of the animals was evaluated using the "open field" test, the formation of spatial working and long-term memory in a radial eight-arm maze, muscle relaxation, imbalance and movements coordination - using the "rotating rod" method. Statistical processing was performed in Microsoft Excel 2016 with AtteStat 12.The results of the study. When comparing the test results of the "open field", "radial labyrinth" and "rotarod" in groups of animals that were administered different doses of the compound, it was found that, in general, these parameters at doses of 2 mg/kg and 5 mg/kg statistically significantly different (increase) from control values, but are similar. At a dose of 10 mg/kg, most of the parameters (except for the rotarod test) for these animals were characterized by a downward trend.Conclusions. The administration of the drug in doses of 2, 5 and 10 mg/kg leads to a decrease in anxious behaviour of animals, which is also accompanied by a pronounced dose-dependent negative effect on the endurance, coordination and memory of animals. The administration of the drug at a dose of 10 mg/kg impaired the learning ability of animals and reduced memory function. This should be considered in clinical studies of the compoun