Body Surface Potential Mapping during Atrial Depolarization in Rats with Post-Infarction Chronic Heart Failure against the Background of Fabomotizole Therapy.

Cardiac remodeling in rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction leads to an atypical location of areas of positive and negative cardioelectric potentials on the body surface before the onset of the P-wave on the ECG in the limb leads, which is a sign of increased heterogeneity of atrial depolarization associated with the appearance of additional excitation focus in the left atrium. A course of therapy with fabomotizole leads to a decrease in the heterogeneity of atrial depolarization at the initial stages of the formation of the cardioelectric field of the atria on the body surface before the onset of the P-wave, thereby producing an antiarrhythmic effect.

Protein Kinase A Inhibitor Attenuates the Antinociceptive Effect of NMDA-Receptor Channel Antagonists in the Capsaicin Test in Mice.

Acute nociceptive pain in mice caused by subcutaneous (intraplantar) injection of TRPV1 ion channel agonist capsaicin (1.6 μg/mouse) and the effects of protein kinase A inhibitor H-89 (0.05 mg/mouse, intraplantar injection) and NMDA receptor channel antagonists MK-801 (7.

Study of the N-(2,3,4-Trimethoxybenzyl)-N-{2-[(2,3,4-Trimethoxybenzyl)Amine]Ethyl}-1,2-Ethandiamine Compound Effect on the Physical Performance of Animals.

We studied the effect of N-(2,3,4-trimethoxybenzyl)-N-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (compound ALM-802) on the physical performance of mice after acute fatigue. The animals' performance was assessed on a treadmill. The criterion for assessing exercise tolerance was the length of the distance passed when running on a treadmill until complete fatigue.

Enhancement of the Clastogenic Effects of Topotecan In Vivo by Tyrosyl-DNA Phosphodiesterase 1 Inhibitors.

Topotecan administered intraperitoneally at single doses of 0.25, 0.5, and 1 mg/kg induced chromosomal aberrations in bone marrow cells of F(CBA×C57BL/6) hybrid mice in a dose-dependent manner.

Correlation of the Left Ventricular Systolic Dysfunction and Ventricular Depolarization in a Post-Infarction Model of Chronic Heart Failure.

The body surface potential mapping of the heart during the period of ventricular depolarization and the inotropic function of the ventricles were studied in rats under conditions of a translational model of post-infarction chronic heart failure developed by us. We revealed a statistically significant (p<0.001) correlation between the left-ventricular ejection fraction and the values of the maximum positive and negative extrema of the cardioelectric field on the body surface of rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction.

Effect of Polyphenolic Composition BP-C2 on Lung Carcinogenesis Induced by Urethane in Progeny of Irradiated Male BALB/c Mice.

We studied the effects of polyphenolic composition BP-C2, comprising molybdenum with lignin derivatives, on lung carcinogenesis induced by urethane in the progeny of F male BALB/c mice preconceptionally exposed to radiation in a dose of 1 Gy. The multiplicity of lung tumors in the progeny of irradiated mice was higher than in the progeny of non-irradiated male parents by 50% in females and 43% in males (p<0.05).

Motor and Cognitive Functions in Aging C57BL/6 Mice: Association with Activity of the Monoaminergic Systems in the Cerebellum and Frontal Cortex.

The activity in the open field, short- and long-term memory in the novel object recognition test, and gait features were evaluated in 6- and 12-month-old male C57BL/6 mice. The levels of norepinephrine, dopamine, serotonin, and their metabolites were determined in the cerebellum and frontal cortex. In the observed age range, a decrease in locomotion speed, impairment of gait initiation and stability, and long-term memory deficit were revealed.

Modeling of the Aqueous Solubility of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a] pyrazine-3-carboxamide: From Micronization to Creation of Amorphous-Crystalline Composites with a Polymer.

N-butyl-N-methyl-1-phenylpyrrole[1,2-a] pyrazine-3-carboxamide (GML-3) is a potential candidate for combination drug therapy due to its anxiolytic and antidepressant activity. The anxiolytic activity of GML-3 is comparable to diazepam. The antidepressant activity of GML-3 is comparable to amitriptyline.

Chronic Ethanol Consumption by Rats before Mating Affects Working Memory in the Offspring.

Parameters of non-spatial and spatial memory were evaluated in sexually mature offspring of outbred rats (females and males F0) consuming a 10% ethanol solution for 30 weeks before mating. We found a significant increase in the recognition index in F1 males and its decrease in F1 females in the novel object recognition test. During the first days of the experiment in T-maze, a decrease in spatial memory was revealed in F1 males, which remained at the trend level until the end of testing; no significant deviations were detected in F1 females.

Changes in Microcirculation in the Brain, Heart, and Liver in Female Rats with Translational Model of Alcoholic Cardiomyopathy.

We studied some features of blood and lymph microcirculation in the brain, heart, and liver of female rats with developed alcoholic cardiomyopathy. In female rats after 24-week forced consumption of 10% ethanol solution, the size and inotropic function of the heart were measured by echocardiography. Microcirculation in the brain, myocardium, and liver was assessed by laser Doppler flowmetry using LAKK-OP2 and LAZMA-D computerized laser analyzers.

Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability.

This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water.

Protective Properties of Spheroidal Taxifolin Form in Streptozotocin-Induced Diabetic Rats.

One of the key factors in the pathogenesis of diabetes and its complications is oxidative stress. To inhibit this process, antioxidants may be helpful. Herein, we focused on the protective properties of taxifolin spheroidal form (TS) in the streptozotocin rat model of diabetes mellitus.

Experimental Study of Antidepressant Properties of Afobazole.

We studied the effects of oral administration of Afobazole in a dose of 10 mg/kg for 5 days on depressive-like behavior of male C57BL/6 mice in the tail suspension test in comparison with amitriptyline (10 mg/kg) or fluoxetine (20 mg/kg) treatment. Afobazole produced an antidepressant effect similar to amitriptyline, but inferior to fluoxetine. The σ1 receptor antagonist BD-1047 in a dose of 5 mg/kg blocked the antidepressant effect of Afobazole, which indicates the involvement of σ1 receptors in the antidepressant effect of the drug.

Specifics of Experimental Modeling 8-OH-DPAT-Induced Perseverative Behavior in Mice.

The effect of 5-HT receptor agonist 8-OH-DPAT (intraperitoneal injection in doses of 1, 2, and 4 mg/kg) on spontaneous alternation behavior of mice in Y-maze was studied without and with habituation procedure and food reward. In the first case, 8-OH-DPAT administration led to a decrease in spontaneous alternation and locomotor activity in mice. At the same time, 8-OH-DPAT treatment after habituation and food deprivation increased repeated choices of goal arms without affecting locomotor activity, which was consistent with perseverative behavior.

To the Mechanism of the Antiarrhythmic Action of Compound ALM-802: the Role of Ryanodine Receptors.

The effect of the compound N-(2,3,4-trimethoxy)-N-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethane-diamine (code ALM-802) on the amplitude of the Ca response in the cell was studied in in vitro experiments. The concentration of intracellular calcium was assessed using a Fura-2 two-wave probe. The experiments were performed on a culture of isolated rat hippocampal neurons.

Analysis of the Involvement of NMDA Receptors in Analgesia and Hypothermia Induced by the Activation of TRPV1 Ion Channels.

NMDA glutamate receptors play an important role in normal and pathophysiological nociception. At the periphery, they can interact with TRPV1 ion channels. The blockade of TRPV1 ion channels decreases NMDA-induced hyperalgesia, and NMDA receptor antagonists suppress the pain response to the TRPV1 agonist capsaicin.

Dynamics of the Cardioelectric Field on the Body Surface during Atrial Depolarization in Rats with Experimental Holiday Heart Syndrome.

In model experiments reproducing the holiday heart syndrome in rats, a discrepancy between the depolarization of the right and left atria has been revealed, which manifested by an atypical arrangement of positive and negative cardiopotentials in the cardioelectric field on the body surface during the P wave and the absence of inversion of the areas of cardioelectric potentials before the onset of P waves in lead II ECG from the limbs.

Damage to Nuclear and Mitochondrial DNA in Different Organs in Streptozotocin-Induced Diabetes Models in BALB/c Mice.

Male BALB/c mice with streptozotocin-induced diabetes mellitus were used to study nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage using comet DNA assay and real-time PCR, respectively. In animals receiving single injection of streptozotocin in a dose of 200 mg/kg, severe hyperglycemia was observed on days 10 and 21 of the experiment, while after 5-fold administration of streptozotocin in a dose of 40 mg/kg, it developed on days 14 and 28. DNA damage and the level of atypical DNA comets in the liver increased both on days 10 and 21 after single administration of streptozotocin, and on days 14 and 28 after repeated administrations.

Nine-month-long Social Isolation Changes the Levels of Monoamines in the Brain Structures of Rats: A Comparative Study of Neurochemistry and Behavior.

Social isolation (SI) is chronic psycho-emotional stress for humans and other socially living species. There are few comparative studies that have measured monoamine levels in brain structures in male and female rats subjected to SI. Existing data is highly controversial.

Mechanisms Underlying the Antiarrhythmic Action of Compound ALM-802.

The mechanisms underlying the antiarrhythmic action of compound trihydrochloride N-(2,3,4-trimethoxy)-N-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethane-diamine (code ALM-802) were studied in vitro. The experiments were performed on a culture of rat hippocampal neurons. The electrical activity of neurons was recorded by the patch-clamp method in the whole cell configuration.

Analysis of the Role of PI3K/Akt Pathway in the Realization of the Normalizing Effect of Low-Molecular-Weight Mimetics of NGF and BDNF on Activity of Prooxidant and Antioxidant Systems in C57BL/6 Mice with Modeled Diabetes.

The effect of low-molecular-weight mimetics of NGF and BDNF (GK-2 and GSB-214 in a dose 0.5 mg/kg, respectively) on malondialdehyde content and activity of an antioxidant defense enzyme glutathione peroxidase was studied in experiments on C57BL/6 mice with streptozotocin-induced diabetes. An increase in the malondialdehyde content indicating enhanced formation of peroxidation products and a decrease of glutathione peroxidase activity in the blood plasma of untreated diabetic animals were revealed.

Сhronically Administered BDNF Dipeptide Mimetic GSB-106 Prevents the Depressive-like Behavior and Memory Impairments after Transient Middle Cerebral Artery Occlusion in Rats.

Background: A dipeptide mimetic of the BDNF loop 4, bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, GSB-106, was designed and synthesized by V.V. Zakusov Research Institute of Pharmacology.

Polymeric Excipients in the Technology of Floating Drug Delivery Systems.

The combination of targeted transport and improvement of the release profile of the active pharmaceutical ingredient (API) is a current trend in the development of oral medicinal products (MP). A well-known way to implement this concept is to obtain floating gastroretentive delivery systems that provide a long stay of the dosage form (DF) on the surface of the stomach contents. The nomenclature of excipients (Es) of a polymeric nature used in the technology of obtaining floating drug delivery systems (FDDS) is discussed.

Relationship between Adenosine Deaminase Activity in the Cerebral Cortex and the Stimulating Effect of Caffeine in Adult Wistar Rats of Different Ages.

The aim of this study was to test the hypothesis that the higher the activity of adenosinedeaminase (ADA) in the brain, the greater should be the motor activity of animals, and possibly the stronger the psychostimulant effect of caffeine. We studied the effect of caffeine (10 and 20 mg/kg) on the motor activity and ADA activity in the frontal cortex of the brain in 2- and 5-month-old rats with different levels of spontaneous motor activity. Total motor activity significantly decreased with age, which was accompanied by a decrease in ADA activity.

Selank, a Peptide Analog of Tuftsin, Attenuates Aversive Signs of Morphine Withdrawal in Rats.

Activity of a peptide tuftsin analogue Selank was studied in outbred rats using the naloxone-precipitated morphine withdrawal model. Single intraperitoneal injection of Selank in an anxiolytic dose of 0.3 mg/kg reduced the total index of morphine withdrawal syndrome by 39.