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Gudasheva T.A.,Research Institute of Pharmacology | Zakusov V.V.,Research Institute of Pharmacology
Vestnik Rossiiskoi Akademii Meditsinskikh Nauk | Year: 2011

The author describes an original approach to the development of dipeptide drugs based on the concept of the leading role of the betabend in the interaction of biologically active endogenous peptides with their receptors. The approachcalled "peptide-based drug design" includes both developments from the structure of a known psychotropic agent toward its topological peptide analog and developments from the active dipeptide site of a neuropeptide toward its mimetic.This strategy has been worked out at the V.V.Zakusov Research Institute of Pharmacology for 25 years. Results of investigations that discovered endogenous peptide prototypes of the known non-peptidic drugs (piracetam and sulpiride) are presented. They provided a basis for the creation of highly active non-toxic oral dipeptide preparations, such as nootrop Noopept, potential antipsychotic Dilept, and potential selective anxiolytic GB-115.

Skurikhin E.G.,Research Institute of Pharmacology | Pershina O.V.,Research Institute of Pharmacology | Reztsova A.M.,Research Institute of Pharmacology | Ermakova N.N.,Research Institute of Pharmacology | And 7 more authors.
PLoS ONE | Year: 2015

Hyaluronidases are groups of enzymes that degrade hyaluronic acid (HA). To stop enzymatic hydrolysis we modified testicular hyaluronidase (HYAL) by activated polyethylene oxide with the help of electron-beam synthesis. As a result we received pegylated hyaluronidase (pegHYAL). Spiperone is a selective D2 dopamine receptor antagonist. It was demonstrated on the model of a single bleomycin damage of alveolar epithelium that during the inflammatory phase monotherapy by pegHYAL or spiperone reduced the populations of hematopoietic stem/progenitor cells in the lung parenchyma. PegHYAL also reduced the levels of transforming growth factor (TGF)-β, interleukin (IL)-1β, tumor necrosis factor (TNF)-α in the serum and lungs, while spiperone reduced the level of the serum IL-1β. Polytherapy by spiperone and pegHYAL caused the increase of the quantity of hematopoietic stem/progenitor cells in the lungs. Such an influx of blood cell precursors was observed on the background of considerable fall level of TGF-β and the increase level of TNF-α in the serum and lungs. These results show pegHYAL reduced the bleomycin-induced fibrosis reaction (production and accumulation of collagen) in the lung parenchyma. This effect was observed at a single and repetitive bleomycin damage of alveolar epithelium, the antifibrotic activity of pegHYAL surpassing the activity of testicular HYAL. The antifibrotic effect of pegHYAL is enhanced by an additional instillation of spiperone. Therapy by pegHYAL causes the flow of CD31-CD34-CD45-CD44+CD73+CD90+CD106+-cells into the fibrous lungs. These cells are incapable of differentiating into fibroblast cells. Spiperone instillation separately or together with pegHYAL reduced the MSC-like cells considerably. These data enable us to assume, that pegHYAL is a new and promising instrument both for preventive and therapy of toxic pneumofibrosis. The blockage of D2 dopamine receptors with the following change of hyaluronan matrix can be considered as a new strategy in treatment of pneumofibrosis. © 2015 Skurikhin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Kseneva S.I.,Research Institute of Pharmacology | Borodulina E.V.,Research Institute of Pharmacology | Semiglazova T.A.,Research Institute of Pharmacology | Kulakova N.V.,Research Institute of Pharmacology | And 2 more authors.
Terapevticheskii Arkhiv | Year: 2011

Aim. To study ways of realization of pleiotropic effects of treatment with low-dose combination of Perindopril arginine with indapamide in hypertensive patients with metabolic syndrome (MS) . Material and methods. Thirty hypertensive patients with MS received low-dose combined drug noliprel A (Servier, France). In weak hypotensive effect noliprel A forte was used. An antihypertensive (by the data of 24-h blood pressure monitoring), sympatholytic (by the levels of ACTH and Cortisol in blood plasma, by variability of the heart rate) and metabolic effects of the drug were assessed after 3 weeks, 3 and 6 months of treatment. Carbohydrate metabolism was studied by glucose and insulin blood levels before meal and after it. Lipid and purin metabolism were assessed by enzyme method, leptin levels - by enzyme immunoassay. Results. 24-h blood pressure monitoring registered a stable regular blood pressure lowering, target blood pressure was achieved in 78.6% patients. Blood ACTH concentration significantly reduced showing a sympatholytic action of the drug. Parameters of lipid, carbohydrate and purin metabolism changed insignificantly. Positive changes were seen in anthropometric indices, leptin tended to decrease. Changes in these parameters, sympatholytic and hypotensive effects depended on plasmic levels of leptin. Conclusion. A fixed low-dose combination of Perindopril arginine with indapamide in a stable hypotensive effect and metabolic neutrality influences some key components of MS including hyperactivity of sympathie autonomic nervous system component and hyperleptinemia.

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