Part I

The problem of heart rhythm disturbances is one of the most urgent topics of modern cardiology. According to the currently available concepts, 1,2- and 1,3-disubstituted aminoindole derivatives, which compound 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1H-indole hydrochloride (SS-68) belongs to, are a promising chemical group in terms of their cardio-pharmacological activit

Benzofurocaine: effects on experimental periodontitis, anti-diabetic activity and molecular mechanisms of action

A promising compound for the treatment of inflammatory periodontal diseases is benzofuracaine (BFC). BFC has pronounced anti-inflammatory, analgesic, reparative, hypoglycemic and other effects. Objective: To assess the influence of benzofuracaine on experimental periodontitis and to study its antidiabetic activity and molecular mechanisms of actio

Role of indole derivative SS-68 in increasing the frequency range of cardiac rhythm control (reflex stimulation of the sinoatrial node)

The substance SS-68 increases the frequency range of heart rhythm control by activating reflex stimulation of the sinoatrial node. The main point of application of SS-68 is the medulla oblongata. Glow in the high-frequency electromagnetic field reflects the process of neuron excitatio

Molecular mechanisms of wound healing: the role of zinc as an essential microelement

Wound healing is a complex multi-phase process consisting of several phases. Each stage involves metal ions, primarily zinc, which stimulates re-epithelialization, decreases inflammation and bacterial growth. The use of known zinc-based drugs is accompanied by side effects and low efficacy due to low skin absorption. These factors significantly limit use of such drugs and highlight the urgency of finding new, more effective and safe treatmen

Study of the selective phenolic inhibitors of arginase 2 acute toxicity

We have previously shown that the isolated arginase 2 inhibitors have a pronounced endothelioprotective level. A strategy is proposed for the targeted search for isolated arginase 2 inhibitors among compounds of a phenolic nature. Received 3 compounds, isolated arginase inhibitors 2. As a result of the study, the acute toxicity of the compounds obtained was studie

STUDY OF INDOLE SS-68 DERIVATIVE IMPACT ON THE PRIMARY GENERALIZED CONVULSIONS INDUCED BY MAXIMAL ELECTRIC SHOCK, THIOSEMICARBAZIDE AND PILICARPINE

Aim. Study of SS-68 impact on primary generalized convulsions in basic estimation tests of anticonvulsant action of agents.Material and methods. Study of the SS-68 impact on primary generalized convulsions included an estimation of anticonvulsant action with maximal electric shock, thiosemicarbazide and pilocarpine antagonism tests performed on white outbred male mice and rats.Results. SS-68 compound possesses dosage dependent anticonvulsant action in maximal electric shock test indicating its ability to prevent death of 100% animals and its activity in thiosemicarbazide and pilocarpine antagonism tests as well. In the maximal electric shock test SS-68 surpassed sodium valproate in its anticolvulsant activity.Conclusion. Neurotransmitter systems of the brain such as GABA, cholinergic and amino acid stimulant system as well as K+, Na+ and Ca2+ channels of neurons shall be the most possible molecular targets of SS-68 anticonvulsant action. Higher activity of SS-68 comparing with sodium valproate in the maximal electric shock test (increasing GABA content in central nervous system) can be related with its wide range of neurotropic action

Influence of different nature cardiotonic medicines on the cytokine system of failing myocardium atthe pressure overload conditions in experimental animals

In the work the efficacy of influence of cardiotonic drugs on the cytokine system changes in the response to acute maximal myocardial pressure overload in congestive heart failure (HF) animals was study in controlled randomized trial. It has been shown, that treatment with Adenocin unlike levosimendan in HF occurs restoration of systolic and diastolic function not only at rest, but also under the acute maximal pressure overload. Therapy with levosimendan at acute pressure overload condition leads to the additional dysbalance in the proinflammatory cytokines and activation of nuclear factor (NF)-kB, as marker of pivotal role of innate immune system in cardiac remodeling under HF. Beneficial action of adenocin on the restoration the balance between pro- and anti-inflammatory cytokine production associated with the normalization of activation of NF-kB that leads to adequate expression of tumor necrosis factor (TNF)-a and interleukin (IL) 1ß in myocardium. Obtained results suggested the hypothesis about acute response of IL6 and in less extent changes in IL 1ß and TNF-a. Thus, adenocin restores myocardium tolerance to pressure overload and reserve ability of immune system, while levosimendan occurs less harmonized action

Efficacy of different cardiotonic drug on severity of endotoxemia under heart failure coupled with systemic inflammatory syndrome in experiments

On the model of systemic inflammatory response syndrome caused by toxi-allergic myocarditis 10-day duration in rabbits the efficacy of 5 days (beginning after 5 days from the injection of staphylococcus toxins) administration of the various pharmacological agents on the endotoxemia intensity has been studied. It has been shown that pathological shifts in cytokine system in myocardium occurs early than in blood. The efficacy of action of the studding cardiotonic drug on the endotoxemia were: Adenocin® > amrinone ≥ digoxin > levosimendan. Influence of Adenocin®, and in less extent digoxin unlike amrinone and levosimendan, leads to the decreasing in the expression of nuclear transcription factor NF-kB and expression of intercellular adhesion molecule-1 (ICAM-1)