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Citation: Galenko-Yaroshevsky PA, Nefedov DA, Zelenskaya AV, Pavlyuchenko II, Chuyan EN, Ravaeva MY, Tkharkakhova NK (2018) Effects of Dimephosphone on skin survival in conditions of reduced blood circulation. Research Results in Pharmacology 4(4): 41-52. https://doi. AbstractIntroduction: The search for and creation of drugs with dermatoprotective and metabotropic activity is one of the priorities of modern diabetology. Synthetic organophosphorus compounds with no anticholinesterase activity, to which Dimephosphone belongs to, deserve great attention in this respect. Materials and Methods:Experiments included 355 white non-linear male mice (18-34 g) and 799 male rats (150-305 g). The dermatoprotective activity (DPA) of Dimephosphone regarding the survival of a skin graft was studied against the background of normoglycemia, as well as against the background of experimental diabetes complicated by hypercholesterolemia. The study of microhemodynamics in the skin was performed using laser Doppler flowmetry. The effects on metabolic processes and the antioxidant system were studied by determining the levels of glucose, urea, creatinine, total bilirubin, total cholesterol, triglycerides, total protein, albumin, globulin, catalase, malondialdehyde, superoxide dismutase, glutathione reductase, glutathione and glutathione peroxidase.Results: Dimephosphone has a pronounced DPA in conditions of reduced blood circulation against the background of normoglycemia and experimental (alloxan) diabetes complicated by exogenous hypercholesterolemia. By DPA, in most cases against the background of normoglycemia Dimephosphone exceeds Actovegine, is comparable to or inferior to Trental and Mexidol, and is more significant in terms of the therapeutic width than all the drugs taken for comparison.Discussion: According to the obtained data , DPA of Dimephosphone may be due to its ability to exhibit significant vasodilating, antihypoxic, antioxidant, antiaggregant, membrane-stabilizing, anti-acidotic, antimicrobial and other properties and also to exert a normalizing effect on carbohydrate, protein, lipid and energy metabolism Conclusion: Dimephosphone can be recommended for further preclinical and clinical studies in the form of various dosage forms, as well as in a combination therapy for metabolic disorders.

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Introduction: The search for and development of new highly active medications and their combinations of the appropriate direction of action remains an urgent problem due to the complications of diabetes mellitus, especially burdened with atherosclerosis, including skin and vascular lesions. Materials and methods: The acute toxicity, histoprotective and dermatoprotective effects of mafusol, rexod, alprostadil and their combinations were studied in male rats with normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Results: The combination of mafusol with rexod is less toxic than mafusol. In arteriovenous insufficiency of the tail, ischemia of the skin fold and skin flap, mafusol (6.25, 12.5 and 25.0 mg/kg in terms of fumarate), rexod (0.01 and 0.02 mg/kg) and especially their combination (6.25 and 0.01 mg/kg) have significant histoprotective, dermatoprotective, hypoglycemic and lipid-lowering effects, both in normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Alprostadil (10 mg/kg) and especially its combination with mafusol (6.25 mg/kg) have a dermatoprotective effect. Discussion: Rexod reduces the acute toxicity of mafusol. The dermatoprotective effect of mafusol, rexod and, to a greater extent, their combination may be associated with increased microhemocirculation, antihypoxic properties and activation of energy processes in the skin, normalization of carbohydrate and lipid metabolism in alloxan diabetes, complicated by exogenous hypercholesterolemia, increased reserve capacity of the antioxidant system, and possibly with the ability of mafusol and rexod to reduce blood viscosity and improve rheological properties of the blood. The combination of mafusol with alprostadil increases the dermatoprotective activity of the latter. Conclusion: Combinations of mafusol with rexod and alprostadil can be recommended for clinical study as dermatoprotective agents for treating traumatic injuries and diabetes mellitus complicated by atherosclerosis.

Using intracellular recording, we studied the effects of N-uronoyl derivatives of an amino acid and peptides (1,2:3,4-di-O-isopropylidene-αa-D-galactopyranuronoyl)-β-alanine (DAGU-Ala), DAGU-glycylglycine (DAGU-Gly-Gly), DAGU-glycyl-D,L-glutamic acid (DAGU-Gly-Glu), as well as of 1,2:3,4-di-О-isopropylidene-αa-D-galactopyranosyluronic acid (DAGU itself), β-alanine (β-Ala), D,L-glutamic acid (D,L-Glu), and glycyl-glycine (Gly-Gly), which were added to the extracellular milieu, on the electrical activity of PPa1 and PPa2 neurons and unidentified neurons of Helix albescens Rossm. DAGU-Gly-Gly applied in concentrations of 10 -4 to 10 -2 М hyperpolarized the membrane in a dose-dependent manner and decreased insignificantly the amplitude of action potentials (APs). Applications of DAGU-Ala, β-Ala, DAGU-Gly-Glu, D,L-Glu, and Gly-Gly in the same doses resulted in a shift of the membrane potential toward depolarization and in a drop in the amplitude of APs. Measurements of the first AP derivatives showed that all the above-mentioned substances suppressed in a concentration-dependent manner both inward and outward transmembrane ion currents. In this case, DAGU suppressed both inward and outward currents, while DAGU-Ala, β-Ala, DAGU-Glu, D,L-Glu, and Gly-Gly inhibited predominantly the outward potassium ion current; DAGU-Gly-Gly inhibited inward sodium and potassium ion currents. Results of a comparative analysis of the neurotropic action of the tested amino acids and their Ν-uronoyl derivatives showed that modification of the molecules of neurotransmitter amino acids leads to a decrease in their neurotoxicity and to an increase in their membranotropic properties. INTRODUCTIONIn search of ways for modulating functions of the CNS, it was found that derivatives of neuroactive amino acids demonstrate a number of special effects; these derivatives can show new properties dissimilar to those of amino acids. It was, e.g., demonstrated that substitution of an amino group in the structure of neuroactive amino acids with a 4-hydroxy-4-methyl-3-tetrahydropyranyl radical leads to the appearance of psychotropic properties in the synthesized compounds [1]. It was reported that choline ethers of L-alanine, L-valine, and γ-aminobutyric acid exert mild antiseizure effects and cause hypothermia [2], while a diethyl ether of L-glutamic acid shows neurotropic properties [3]. In this respect, special interest attaches to combinations of neurotropic amino acids (or oligopeptides) with N-1,2:3,4-di-О-isopropylideneαa-D-galactopyranosyluronic acid (DAGU). It was found that novel N-uronoyl derivatives of amino acids, such as N-(1,2:3,4-di-O-isopropylidene-αa-D-galactopyranuronoyl)-β-alanine (DAGU-Ala), DAGU-glycyl-D,L-glutamic acid (DAGU-GlyGlu) and DAGU-glycyl-glycine (DAGU-Gly-Gly), possess clearly pronounced neurotropic effects [4]. However, the mechanisms underlying such effects remain unstudied. This is why our work was aimed at obtaining the corresponding data. METHODSWe recorded the activity of 118 neurons of the parietal ganglion (65 PPa1 ...

The paper researches the effect of cobalt (ACCo2+) and zinc (ACZn2+) acetylsalicylates in doses of 5 and 10 mg/kg on the characteristics of the rats’ cardiorespiratory system. It is ascertained that coordinating metal compounds with the acetylsalicylic acid have a more pronounced biological effect in comparison with a monocompound of the acetylsalicylic acid; this makes the further search for coordinating compounds’ effects more prospective.

Peculiarities of rat behavior were studied on a series of experimental stress models after systemic administration of new N-uronoyl derivatives of amino acids. The psychotropic effect was shown to be determined by the nature of the amino acid fragment. N-(l,2:3,4-di-O-isopropylidene-alpha-D-galactopyranuronoyl)-glycylglycine exhibited a more pronounced anxiolytic effect than pyracetam, whereas N-(l,2:3,4-di-O-isopropylidene-alpha-D-galactopyranuronoyl)-glycylglutamic acid is a stronger antidepressant than amitriptyline. Mechanisms of the psychotropic effects of the examined derivatives are discussed.

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