Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, primarily their HCN4 subtype, are one of the promising targets for the development of cardioprotective agents. HCN channel blockers have a selective bradycardic effect, preserving myocardial contractility and diastolic function and not affecting the electrophysiological parameters of the heart. This review continues a series of reviews on the analysis of compounds with cardioprotective properties in a number of biaromatic structures, which include a wide range of HCN channel blockers.

Oxidative stress plays a key role in epileptogenesis. The aim of the study was to evaluate the effect of seizures on the development of oxidative stress and the presence of antioxidant properties in carbamazepine and valproic acid in convulsive state caused by maximal electroshock seizure (MES). Methods. An electroconvulsive seizure were induced by the MES-test in mice, with assessment of the severity of seizures on a point scale. Oxidative stress was assessed by products of lipid peroxidation (LPO) determined in blood plasma. Results. It has been established that exposure to MES followed by tonic-clonic seizures leads to oxidative stress in mice. Valproic acid and carbamazepine completely protected against seizures after MES-test, however, the concentration of lipid peroxidation products did not differ from the MES group and was also higher than in the control group.

The distribution kinetics of a compound with cardioprotective activity, N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino] ethyl}-1,2-ethanediamine (ALM-802) in rat tissues and organs after single intragastric administration at a dose of 100 mg/kg. The values of ALM-802 tissue availability were determined. Tissue availability of ALM-802 falls in a row: kidneys→liver→heart→spleen→skeletal muscle→brain (129.3; 27.2; 20.9; 15.3; 5.9 and 0.3, respectively). It was found that ALM-802 is excreted from the body rather slowly: k_el values ranged from 0.0252 to 0.0885 h^–1, MRT values were 7.6–59.3 h.

Effect of Pantogam active subchronic administration (200 mg/kg/day, i.p.) on the behavior of outbred CD-1 mice in the experimental model of attention deficit disorder was studied in the "closed enriched cross maze" test. Pantogam active corrected the initial attention deficit of ED-low rodents subpopulation without changing other parameters of their behavior. Analysis of the results of radioligand binding revealed statistically significant differences in the distribution of D₂ and GABA_B-receptors in the brain structures of outbred CD-1 mice subpopulations. In the prefrontal cortex (PFC) of ED-low control group with reduced attention level, compared with ED-high control, density of D₂ receptors was higher by 18 %, while density of GABA_B receptors was lower by 35 %. Administration of pantogam active resulted in decreasing of D₂ receptors density by 23 % and increasing of this indicator by 42 % for GABA_B- receptors in the PFC of ED-low animals, respectively. Thus, this studied drug has potential efficacy in treating attention deficit in experimental animals, normalizes behavior and possible molecular markers of this pathology.

The investigation purpose was to study the effect of fabomotizole on blood microcirculation in intact and ischemic myocardium in conditions of acute ischemia of the heart muscle. The experiments were carried out on anesthetized (urethane, 1300 mg/kg, i.p.) white mongrel male rats weighing 220–250 g. Acute myocardial ischemia was caused by occlusion of the left coronary artery. Blood microcirculation was evaluated by laser Doppler flowmetry using a computerized laser analyzer "LAKK-OP2". It was found that fabomotizole (15 mg/kg, i.v.) in an intact heart does not affect blood microcirculation. Immediately after coronary artery ligation in the myocardial ischemia zone, microcirculation decreases sharply (by about 30 %, p = 0.0106) and practically does not change in the conditionally intact myocardium. Fabomotizole, administered 5 minutes before occlusion of the coronary artery, prevented a decrease in microcirculation in the ischemiс zone of the myocardium. The ability of fabomotizole in conditions of acute myocardial ischemia to prevent a decrease in the level of microcirculation in the ischemic zone may contribute to the anti-ischemic activity of the drug.

Porphyrias are the group of orphan diseases, related to pathological disruptions of heme biosynthesis. These diseases are hard to diagnose timely and existing methods lack universality. High performance liquid chromatography coupled with ultraviolet detector could be adapted for this purpose via determination of porphyrins in human urine. Waters Acquity UPLC H-CLASS with diode matrix was used in this study. Developed method allows determining the inner standard and 9 biomarkers, each connected to specific stage of heme biosynthesis. Developed method is validated for porphyrias diagnosis.

Relevance. The use of gene therapy drugs for the treatment of genetic diseases and stimulation of regeneration processes is lengthy and involves repeated injections, which may lead to increased dissemination of gene therapy constructs from the injection site and undesirable ectopic expression of growth factors encoded in them. Existing approaches to study the pharmacokinetics of a drug to assess the dissemination of a gene therapy drug from the site of administration are not applicable. Objective: to evaluate the suitability of the real-time PCR method for studying the biodistribution of a promising gene therapy drug in mice during a course of use. Methods. Male F1 CBA×C57/Black mice after nerve injury were injected with the test plasmid into the denervated tibial muscle after nerve injury, as well as after 4, 9 and 13 days at a dosage of 60 and 120 μg/mouse. After 7, 14, and 28 days, organ and tissue samples were removed, total DNA was isolated, and plasmid DNA content was assessed by real-time PCR. Results. We have shown that the studied genetic construct is able to disseminate from the injection site. We have found that the peak of dissemination for this construct in the organs and tissues of the mouse is reached 14–28 days after the end of the course application, while ectopic expression of growth factors is not observed in them. Conclusion. The proposed method is specific, highly sensitive, and linear over a wide range of concentrations. Thus, it can be recommended for studying the biodistribution of potential gene therapy drugs in the body of experimental animals as part of a preclinical studies complex.