[To the mechanisms of antiarrhythmic action of Allapinine].

Allapinine (lappaconitine hydrobromide) is a drug for the treatment of cardiac arrhythmias, it shows IC class antiarrhythmics properties. Its action mechanism is associated with blockade of Na(+)-channels with subsequent inhibition of the depolarization rate and, consequently, of the slowing and reducing the excitability of the cardiac conduction system. At the moment, it is not established, what factors are associated with side effects of Allapinine, and therefore it seems important to study the molecular mechanisms of its action. The target genes were identified in a rat model of aconitine-induced arrhythmia using a commercial kit "Rat Neuroscience Ion Channels & Transporters RT2 Profiler PCR Array" (SABioscienses). Comparison of the expression of 84 genes in the experimental (aconitine arrhythmias/Allapinine) and control (aconitine arrhythmias/saline) animals revealed changes in the mRNA level of 18 genes. It has been shown an increase in mRNA levels of genes encoding various types of K(+)-channels (kcna6, kcnj1, kcnj4, kcnq2, kcnq4), Ca(2+)-channel (cacna 1g), vesicular acetylcholine transporter (slc 18a3). Decrease in the mRNA level was observed for genes encoding the Na(+)-channel (scn8a), K(+)-channels (kcne 1, kcns 1), membrane transporters (atp4a, slc6a9). Taken together, it appears that the effect of Allapinine on aconitine--induced arrhythmias is due to modulation of genes encoding Na(+)-, K(+)-, Ca(2+)-channels, conducting ionic currents (I(Na), I(to), I(Ks), I(K1), I(CaT)), which are involved in the formation of different phases of the action potential. The effect of the drug on the mRNA levels of genes encoding the acetylcholine and glycine transporters, suggesting the participation of these neurotransmitters in the mechanisms of anti-arrhythmic properties of the Allapinine.

[Animal in vivo model of arrhythmia for genes target identification for 5-amino-exo-3-azatricyclo[5.2.1.0(2,6)]decan-4-one].

The goal of the current work is to study the molecular mechanisms underlay the action of 5- amino-exo-3-azatricyclo[5.2.1.0(2,6)]decan-4-one (P-11) with combined antiarrhythmic, nootropic, anti-inflammatory and anaesthetic activities. The aconitine-induced experimental rat model of cardiac arrhythmia has been used in our study. Aconitine was administered once intravenously in a dose 50 microg/kg whereas experimental animal group received P-11 in a dose 0.3 mg/kg (the compound was injected intravenously 2 min before acute aconitine treatment). Expression macroarray (Atlas Rat cDNA Expression Array, #7738-1; BD Biosciences) was used to identify the target genes for P-11 compound. Comparative analysis of changes in the status of expression of genes in the heart of rats induced by P-11 against the simulated in vivo arrhythmia identified 16 genes that reproducibly alter the level of expression.These genes encode the extracellular matrix proteins (glypican 1, Gpc1; tissue inhibitor of metalloproteinase 2, 3, Timp2, Timp 3); intracellular signaling molecules (rho GTPase activating protein 7, Dlc1; protein tyrosine phosphatase 4a1, Ptp4a1; phosphodiesterase 4D, PDE4D; PI3-kinase regulatory subunit alpha, PIK3R1; guanine nucleotide binding protein alpha 12, Gna12) and protein of intermediate junctions (junction plakoglobin, Jup), proteins involved in glycolysis (phosphofructokinase I, Pfk1) and hemostasis (tissue plasminogen activator, Plat), plasma membrane transporters (Solute carrier family 16, member 1, Slc16a1; ATPase, Na+/K+ transporting, Atp1a), and ets. (c-fos protooncogene, c-fos; telomerase protein component 1, tlp; Annexin 1, anxa 1). Thus, the data about the selective effect of P-11 on genes whose products are involved in the aritmogenesys mechanisms, allow us to consider this compound as a promising means of pathogenetically oriented pharmacotherapy of cardiac arrhythmias.

[Hepatoprotective effect of 2-demethoxycarbonyl-2-ethoxycarbonyl-11-deoxymisoprostol].

2-Demethoxycarbonyl-2-ethoxycarbonyl-11-deoxymisoprostol (11-DMP) produces antioxidant effect on the models of toxic hepatitis induced by paracetamol and carbon tetrachloride. The drug normalizes the lipid peroxidation (LPO) prosess in rat liver of the rat and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the rat blood, thus demonstrating hepatoprotective action.

[Pharmacological properties of 11-deoxymisoprostol]. / Farmakologicheskie svoistva 11-dezoksimizoprostola.

11-Deoxymisoprostol showed gastroprotector activity on the acute models of ulcers induced by acetylsalicylic acid and ethanol and produced curative effect on the chronic ulceration model induced by acetic acid. The positive effect is manifested by a decrease in the number of destructions and in the total area of chronic damage in the mucous membrane of the stomach. In addition, 11-deoxymisoprostol showed antiphlogistic activity on the acute edema models induced by carrageenan and formalin, by decreasing the model foot edema growth in experimental animals. The drug also decreased the level of lipid peroxidation in the rat blood serum on the background of acute ethanol ulceration.