Search

Aim. This study was aimed at searching and investigating new substances among phenylethyl derivatives of 3-hydroxypyridine, which exhibit a high actoprotective activity under the conditions of normoxia and acute hypobaric hypoxia.Materials and methods. New compounds of phenylethyl derivatives of 3-hydroxypyridine under the SC code (n = 23) were investigated in comparison with bemethyl and bromantane. The actoprotective activity of new compounds was assessed in experimental animals using a treadmill running test under the conditions of normoxia and acute hypobaric hypoxia. The studied chemical substances and comparative drugs were administered 1 hour prior to exposure of animals to the test. Statistical processing of the obtained experimental results was performed using Microsoft Excel and Statistica for Windows 6.0 software.Results. Among the studied substances, active compounds exhibiting an actoprotective effect have been distinguished. SC-119 chemical substance was revealed, which exceeds the other studied chemicals and bemethyl and bromantane reference actoprotectors in terms of the range of effective doses and actoprotective activity under the conditions of normoxia and acute hypobaric hypoxia.Conclusion. According to the results of the study, the SC-119 compound seems to be a prospective candidate for further research into highly effective actoprotective drugs.

Increasing physical performance is an urgent task for pharmacology and practical medicine since a decrease in physical performance is a common symptom of many acute and chronic diseases. The aim of this work is to study the effect of monoterpenoid derivatives with 3,7-diazabicyclo [3.3.1] nonane (bispidine) on the physical performance of mice. Physical endurance was studied in two tests: Porsolt forced swimming test with a load of 7% of body weight and running on a treadmill. To assess the effect of the investigated agents on locomotor activity, an open field test was performed. As a result, it was found that, of the two compounds with the codes K1-456 and K1-458, the most effective increase in running and swimming duration is compound K1-458, containing residues of (-) - myrtenal linked to the bispidine moiety through the amino group, at a dose of 100 mg/kg after a single intragastric administration. It was also found that the studied agents statistically significantly increase locomotor activity, distance traveled, speed and reduce the time of the stationary moment when testing in the "open field". Thus, derivatives of bispidine containing monoterpenoid residues are a promising new class of organic compounds for the search for new drugs to increase health.

New structural analogs of bromantane with greater conformational lability than the prototype were synthesized. Their physiological activity profiles were assessed in vivo. It was found that the analogs could be prepared under much milder conditions than bromantane and that their biological activity profiles dependedstrongly on the nature of adamantane substitution.

Neurotoxicological profile of actoprotector bromantane was studied on rats using S. Irwin's protocol of multi-test observation. The drug in doses of 30-300 mg/kg stimulated and in doses of 600-9600 mg/kg suppressed behavioral activity. Spontaneous motor activity increased after single treatment with bromantane in doses of 30-300 mg/kg, did not change after treatment in doses of 600 mg/kg, and was inhibited after treatment in doses above 600 mg/kg. In doses of 300-600 mg/kg the drug reduced pain sensitivity threshold and in doses above 600 mg/kg elevated the pain threshold and tactile sensitivity and reaction to knock. Bromantane induced mydriasis in all studied doses; in doses above 10 g/kg the preparation induced blepharoptosis. In doses above 5 g/kg bromantane slightly increased respiration rate and depth (Kussmaul-like respiration). In some animals bromantane in high doses induced regurgitation, diarrhea, and polyuria. Rectal temperature decreased by 0.5-1°C after virtually all doses. Behavioral effects of bromantane in doses of 30 and 600 mg/kg were associated with stimulation of the central dopamine and suppression of muscarinic and nicotinic cholinergic structures, n-cholinolytic effects of bromantane was more pronounced at a dose of 30 mg/kg than at a dose of 600 mg/kg.

The adamantane derivatives adapromine, midantane, and bromantane modify bioelectrical activity of brain cortex and subcortical structures. Neurophysiological effects of these preparations indicate that they possess psychostimulating activity. The effect of bromantane on electrical potentials from left and right sensorimotor cortex, dorsal hippocampus, and lateral hypothalamus was stronger than that of adapromine and midantane. This effect was observed as greater quantitative changes in the characteristics of electroencephalogram and changes practically in all characteristics of the power spectrum of electroencephalogram.

Oxidative processes in the bile caused by congestion lead to bile restructuring consisting in decreased phospholipid content paralleled by increased content of their peroxidation products and shifts in relative composition of components toward the predominance of more hydrophobic ones, which is more pronounced in calculous bile during incubation.

The purpose of this study was to develop and validate a high-performance liquid chromatographic–tandem mass spectrometric (LC–MS/MS) method for analysis of the bromantane in human plasma. The analyte and Internal Standard (IS), selenox, were extracted from human plasma by solid-phase extraction and separated on a Zorbax SB-C18 column using methanol–0.2% formic acid as mobile phase. Detection was performed using an atmospheric pressure chemical ionization source and mass spectrometric positive Multi-Reaction-Monitoring-Mode (+MRM) at an ion voltage of +2000 V. The assay was linear over the concentration range 1–500 ng/mL with the Lowest Limit of Quantification (LLOQ) of 1 ng/mL. The method also afforded satisfactory results in terms of the sensitivity, specificity, precision (intra- and inter-day, CV

It is shown that there is a mathematical correlation between an integral characteristic of activity of the organism (the capacity for work), electrophysiological indexes of functioning of the brain structures, and the concentration of a novel derivative of 2-aminoadamantane, bromantane, in the brain. The nature of the correlation between integral characteristics of the organism studied on different levels is found to change depending on the time elapsed from the administration of the preparation and on its concentration in the blood or target tissue.

Bromantane (2[n-bromphenyl]aminoadamantane) in doses of 40–60 mg/kg had no effect on spontaneous motor activity of BALB/c mice in a Optovarimex apparatus and prevented freezing in the open field test, but stimulated motor activity in C57B1/6 mice. It is concluded that psychostimulatory and anxiolytic effects are present in the spectrum of the pharmacological activity of bromantane.

It is demonstrated that bromantane induces a pronounced and prolonged (8 h) increase in the release of dopanime. Tetrodotoxin (10−6 M) perfused via a microdialysis probe partially inhibits the bromantane-induced release of dopamine. The extracellular content of the dopamine metabolites 3,4-dioxyphenylacetic and homovanillic acids is slightly decreased. The possible mechanisms of action of bromantane on the dopamin- and serotoninergic systems of the brain are discussed.