Use of peptide gly-his-lys for anxiolytic effect. RU patent 2480232.
SUBSTANCE: invention refers to medicine, namely physiology, pathophysiology and pharmacology, and may be used for an anxiolytic (antianxiety) effect. Substance of the invention consists in the use of peptide Gly-His-Lys of formula (NH2)Gly-His-Lys(COOH) for the anxiolytic effect. The experimental use of peptide Gly-His-Lys in single doses of 0.5 and 5 mcg/kg of body weight 12 minutes before the beginning of the examination causes the manifested anxiolytic effect.
EFFECT: invention provides the use of peptide Gly-His-Lys by the new application, namely for anxiolytic action. The invention relates to medicine, namely to physiology, pathophysiology and pharmacology, and can be used for anxiolytic () effect. In the literature a number of researchers describes the properties of the peptide Gly-His-Lys. The modulatory effect of the regulation of processes of growth and differentiation of cells (Kato, K. Kasai S., Onodera K. et al. Effect of hepatocyte growth factor on the proliferation of transplanted hepatocytes in the spleen // Transplant. Proc. - 1997. - Vol.29, N 4. - P.2029-2031; Sporn M.B., Roberts A.B. Transforming growth factor-in: recent progress and new challenges // J. Cell Biol. - 1992. - Vol.119, N 5. - P.1017-1021). A number of studies have confirmed the influence of peptide as a stimulator of the wound healing, because it is known for its stimulating effect on the synthesis of collagen and fibroblasts (Maquart F.X., Bellon G., Chaqour Century et al. In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds // J. Clin. Invest. - 1993. - Vol.92, N 5. - P.2368-2376).
It is shown that Gly-His-Lys contributes to stimulation of physiological and reparative regeneration of the liver (Smakhtin M. et al Atlas, I.A., Hemp A.A., Б I.I. the Method of stimulation of physiological and reparative regeneration of the liver. - The patent for the invention №2214269, 20.10.2003,). Known to the stimulating effect of peptide on hair growth (Trackhy R.E., Fors T.D., Pickart L., Uno H. The hair follicle-stimulating properties of copper peptide complexes. Results in C3H mice // Ann. N. Y Acad. Sci. - 1991. - Vol.642, N 10. - P.468-469) and anti-inflammatory effect associated with a decrease in the allocation of iron of ferritin in the damaged tissues (Miller D.M., DeSilva D., Pickart L., Aust S.D. Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation // Adv. Exp. Med. Biol. - 1990. - Vol.264. - P.79-84).
Also, set the analgesic effect of Gly-His-Lys with pain caused by temperature irritation ( of M.E. Ter-Minassian, Б I.I., Smakhtin M. et al Atlas and other Use of peptide Gly-His-Lys for analgesic effect with pain caused by temperature irritation. - The patent for the invention №2421235, 20.06.2011,). The technical result of the invention is new usage of peptide Gly-His-Lys with formula (NH2 )Gly-His-Lys(COOH), for the anxiolytic effect. The technical result of the invention is attained by application of peptide Gly-His-Lys for anxiolytic effect. Currently known as chemical formula of this peptide, it can be synthesized in a laboratory synthesis of peptides or bought from companies involved in the delivery of biologically active compounds (Sigma, ICN, Merk, Bachim and others). We used the drug first synthesized in Institute of chemistry of St. Petersburg state University.
Dissolved in izotonicescom solution of sodium chloride peptide Gly-His-Lys impose experimental animals (rats) parenteral (injected) once in doses of 0.5 and 5 mg/kg body weight 12 minutes before the start of the study.
Specific example of the Experimental animals (rats-males Wistar) weighing 200-250 g were divided into groups of 10 animals each (table). Animals were kept at room temperature 22-24 C, light mode: 12 hours of light and 12 hours - darkness, and received a standard granulated food and water in the public domain.
In the experiment, the anxiolytic effect of drugs commonly assessed by the method uplifted cruciform labyrinth (Voronin T.A., S.B. Seredenin Kiryukhina trankviliziruyuschego (anxiolytic) actions pharmacological substances // Hands-on experimental (pre-clinical) study of new pharmacological substances / Under the General Ed. Corr. Russian Academy of medical Sciences, Professor ... - M: Medicine, 2005. - S.257-258). In this method, the increase in the number of visits in the open (bright) sleeve maze and increase in the time spent there the animal without increasing the overall motion activity indicate the presence of the anxiolytic effect of the drug. To study anxiolytic activity of rats were placed on a unit consisting of the cross diverging from the Central platform of the right-angle 4 bags (two opposite, open, without walls and two closed, dark). Sleeve length - 50 cm, width - 14 cm, height of the walls closed sleeves - 30 cm, height of the Board of open sleeveless - 1 see the maze was installed on the cart with jammers, providing rise of the arena to a height of 50 cm above the floor level.
Experiments were performed in normal lighting. Immediately before the start of the study of animals kept for 5 min in dark cells. Then the rat was placed in the elevated plus maze to the Central site head to the open sleeve and within 5 minutes we registered the time of stay of an animal in the public, private, sleeves, on the Central stage, the number of visits in open and closed sleeves.
Anxiolytic effect was estimated to increase the number of visits in the open (bright) sleeve of the maze and increase the time spent there the animal (in seconds) with no increase in total physical activity. Peptide Gly-His-Lys was dissolved in izotonicescom solution of sodium chloride to obtain the necessary doses of 0.5 and 5 mg/kg body weight of the animal. Administered parenteral (injected) once experimental animal in the amount received at the rate of 1 ml per 1 kg of body weight (0.3 ml), 12 minutes before the start of the study.
Control animals received an equivalent volume of a physiological solution (FR). When using peptide Gly-His-Lys in doses of 0.5 and 5 mcg/kg marked anxiolytic effect (table). Thus, the results of the experimental studies show that the use of peptide Gly-His-Lys in doses of 0.5 and 5 mg/kg caused a pronounced anxiolytic effect. This method is based on application of regulatory peptide belonging to class of biologically active substances with strong effect and , is not time consuming and requires the use of sophisticated machinery. Application of peptide Gly-His-Lys with formula (NH2 )Gly-His-Lys(COOH), for the anxiolytic effect.