Reviews on Clinical Pharmacology and Drug Therapy

At the beginning of the 21st century, Professor Aleksandr Urakov and his colleagues from Russia discovered oxygen-producing antihypoxants and a method to alleviate tissue ischemia and/or hypoxia by injecting solutions of these agents directly into affected tissues. During the development of this research area, the team secured approximately 40 patents for related inventions. Oxygen-producing antihypoxants include warm alkaline hydrogen peroxide solutions (WAHPSs), which, upon injection into sputum, mucus, pus, blood, or other tissues, rapidly convert them into a soft oxygen foam. This occurs because many bodily tissues contain the enzyme catalase, which, in an alkaline environment under hyperthermic conditions, accelerates the decomposition of hydrogen peroxide into water and molecular oxygen by millions of times. Catalase-mediated cleavage of the H₂O₂ in 100 mL of a 3% hydrogen peroxide solution yields approximately 1.408 g of molecular oxygen, which, at standard atmospheric pressure, occupies a gaseous volume of about 1 L. Based on these findings, the researchers proposed intrapulmonary, endotracheal, or endobronchial administration of WAHPSs to rapidly oxygenate blood via the lungs in cases of severe acute respiratory obstruction due to asphyxia from sputum or blood. In experimental models of severe acute asphyxia induced by sputum or blood, a single intrapulmonary, endotracheal, or endobronchial injection of WAHPS transformed colloidal masses in the respiratory tract into soft white oxygen foam within 1–2 seconds, initiating blood oxygenation and fully resolving hypoxemia within 12 seconds. These theoretical and experimental results indicate that intrapulmonary, endotracheal, and endobronchial WAHPS injections could serve as an alternative to gaseous oxygen in mechanical ventilation or extracorporeal membrane oxygenation for treating patients with severe acute respiratory obstruction and hypoxemia.

This review discusses the problems of glutamate excitotoxicity, the contribution of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists to the treatment of central nervous system diseases, and presents the results of in vivo experiments with a new class of combined (NMDA + AMPA) glutamate open-channel antagonists. They are structures containing a tetra-, penta-, or hexamethylene chain with two ammonium groups at the chain ends, one of which is an unsubstituted amino group, and the other includes an adamantyl or a 1-phenylcyclohexyl radical. This review discusses the strategy for discovering new glutamate antagonists, in particular, a comparison of the efficacy of allosteric blockers (perampanel) and open-channel ion blockers. The latter are preferred because the breadth of their therapeutic window is 2–3 orders of magnitude wider. Increased activity (along with decreased toxicity) is observed when moving from monocationic to dicationic structures. The review notes the versatility of the effects of combined (NMDA + AMPA) antagonists, which have demonstrated therapeutic efficacy in models of epilepsy, parkinsonism, depression, pain, hypoxia, and multiple sclerosis. The ability of this group of antagonists to inhibit excitotoxicity explains their broad range of therapeutic properties. Combined (NMDA + AMPA) blockers offer broad variability in therapeutic effect, as they allow for the selection of an antagonist with the required ratio of NMDA and AMPA contributions for a specific therapeutic purpose.

BACKGROUND: Food addiction is an urgent problem. The formation of food addiction involves effects on the reward system similar to those of narcotic substances. Glutamatergic inputs can modulate the activity of the mesolimbic dopamine system of the brain, thereby affecting the reward system. In this study, we investigated the mechanism of action of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist on the manifestation of compulsive overeating and on stress-activated eating behavior.

AIM: To study the efficacy of the GluA1 AMPA receptor antagonist IEM-1460 in a model of compulsive overeating and to evaluate its antagonistic activity against glutamate AMPA receptors.

METHODS: Experiments were conducted in vivo on Wistar rats and in vitro on isolated Danio rerio neurons. IEM-1460 (3 mg/kg, intraperitoneally) was studied in a model of compulsive hyperphagia with restricted access; stress was induced by electrical foot stimulation (foot-shock). The effect of IEM-1460 on ion currents induced by application of kainic acid (an AMPA receptor agonist) was studied on isolated Danio rerio neurons using the patch-clamp technique.

RESULTS: In the model of compulsive hyperphagia with restricted access, administration of IEM-1460 reduced food intake to 10.0 ± 0.9 g, which was significantly lower than the values without additional exposure (15.9 ± 0.5 g) and after foot-shock stimulation (18.6 ± 0.9 g). In vitro, IEM-1460 had a blocking effect on AMPA glutamate receptors in the patch-clamp assay.

CONCLUSION: These findings highlight the important role of glutamate AMPA receptors in the formation and maintenance of food addiction. The GluA1 AMPA receptor antagonist IEM-1460 shows high efficacy in the model of compulsive hyperphagia in rats after foot-shock stress, which activates eating behavior. Pharmacological agents based on AMPA receptor antagonists may be effective for correcting compulsive hyperphagia induced by psychogenic stress.

BACKGROUND: Our previous studies demonstrated that administration of extracts of Cordyceps militaris (L.) Fr. biomass and culture fluid resulted in significant changes in blood pressure and heart rate in rats. However, the effect of these fungal biotechnological products on microcirculation has not been studied.

AIM: To determine changes in microcirculation parameters in rats exposed to C. militaris (L.) Fr. extracts.

METHODS: The study used 30 male Wistar rats weighing 250–300 g, which were divided into three groups of 10 animals each. Group 1 served as a control; animals in group 2 received 0.5 mL of C. militaris culture fluid extract, and group 3 received 0.5 ml of C. militaris (L.) Fr. biomass extract. Microcirculation was studied using laser Doppler flowmetry with a Lazma-MC laser blood flow analyzer (second version). Both non-oscillatory and oscillatory parameters of tissue microhemodynamics were recorded.

RESULTS: Intraperitoneal administration of an extract of the in vitro–obtained mycelial biomass of C. militaris (L.) Fr. (group 3) resulted in a 30.3% increase in tissue perfusion (p = 0.0026) due to increased endothelial metabolic activity, decreased sympathetic adrenergic pressor effects, and decreased precapillary sphincter and precapillary metarteriole tone resulting from Ca²⁺-dependent muscle relaxation. This was evidenced by significant increases in all oscillatory and non-oscillatory parameters of microcirculation. Following administration of C. militaris (L.) Fr. culture fluid extract (group 2), perfusion increased by 32.6% (p = 0.0016), endothelial rhythm by 55% (p = 0.0072), neurogenic rhythm by 77.9% (p = 0.0121), myogenic rhythm by 82.1% (p = 0.0099), and respiratory rhythm by 45.5% (p = 0.0370) compared to those in the control group, indicating the development of vasodilation. The vasotropic effects in groups 2 and 3 were comparable; however, the effects of C. militaris were somewhat more pronounced in group 2, which was attributed to the different concentrations of dry matter and biologically active substances in these biotechnological products.

CONCLUSION: Thus, as the analysis of the study results showed, the administration of C. militaris to animals in groups 2 and 3 led to endothelium-dependent vasodilation, a decrease in peripheral resistance, an increase in blood flow into the nutritive microvascular bed, and improvement in venous outflow.

BACKGROUND: Over the past decades, many countries have experienced a significant increase in antimicrobial resistance among pathogens. This greatly complicates the selection of optimal antimicrobial therapy (AMT) regimens, which are important for treating individual patients and for the functioning of the healthcare system as a whole. In this context, one possible tool for rationalizing AMT is conducting prospective epidemiological studies to monitor antimicrobial resistance.

AIM: To study actual prescribing practices for antimicrobial therapy in complicated urinary tract infections in the Bryansk region.

METHODS: This prospective study analyzes data collected through patient interviews, medical record review, and the regional medical information system for patients who received outpatient or inpatient care at Bryansk Regional Hospital No. 1 from 2022 to 2025. The study included 147 cases of complicated urinary tract infections (cUTIs) in 133 patients.

RESULTS: According to previous studies, combination AMT regimens have demonstrated the greatest efficacy in cUTI. In complicated infections, particularly hospital-acquired infections or those with previous AMT exposure, the efficacy of fluoroquinolones and third-generation cephalosporins as monotherapy declines sharply. The most frequently prescribed initial therapy for cUTI included parenteral third-generation cephalosporins (44.2%), third-generation aminoglycosides (29.9%), fluoroquinolones (22.4%), carbapenems (14.9%), and beta-lactamase inhibitor-protected aminopenicillins (13.6%). In immunocompromised patients, cUTI are often caused by rare and atypical pathogens, particularly gram-positive bacteria. Therefore, it is recommended that these patients receive AMT regimens that include drugs with the broadest possible spectrum of activity.

CONCLUSION: When selecting AMT, age-related functional and morphological changes of the urinary system should be considered. A promising direction is the development of algorithms for switching from parenteral to enteral administration of antimicrobial agents in patients with cUTI, which would improve long-term outcomes by shortening hospital stay and reducing the risk of catheter-associated infections. In regions with a high prevalence of fluoroquinolone-resistant and extended-spectrum beta-lactamase-producing E. coli strains (> 10%), initial empirical therapy with aminoglycosides or carbapenems is recommended until susceptibility data to other antimicrobial agents are available.