Selank

A synthetic derivative of the endogenous peptide tuftsin heptapeptide selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) possesses an anxiolytic and psychostimulant effect, and represents a working element of a new peptide drug having completed the third phase of the clinical testing as a selective anxiolytic. The neurobiochemical spectrum of selank action combines mechanisms which are characteristics of antidepressants and psychostimulants: activation of the brain monoaminergic systems, dopamine synthesis and turnover, and modulation of the tyrosine hydroxylase activity...

The purpose of this article was to study the immunotropic effects of the new neurotrophic heptapeptide selank. The experiments in vitro revealed that the drug in concentration 10-7 M completely suppressed gene expression by peripheral blood IL-6 of patients with depression but not of the healthy controls. At the same time, the significant increase (p<0,05) of IL-6 concentration was observed in the cell culture of peripheral blood of patients in the presence of selank. The changes of the Th1/Th2 cytokine balance in vivo were found in the serum of patients with generalized anxiety disorder and neurasthenia who received Selank during 14 days...

It has been shown that the peptide anxiolytic drug Selank recovers learning and memory impaired by damage of the noradrenergic (NA) brain system in Wistar rats after injection of the NA-synthesis inhibitor disulfiram, administration of neurotoxic compound 6-OHDA, or a combined induction of hypoxic hypoxia and hypercapnia. The main component of the Selank action is the stimulation of the search reflex aimed to distinguish an adequate adaptive response in the first trials of the learning session. The enhancement of memory consolidation and retrieval shows evidence for stimulation of the brain motivation mechanisms impaired by the NA system damage...

Sixty-two patients with generalized anxiety disorder (GAD) and neurasthenia were studied. The effect of selank (30 patients) was compared to that of medazepam (32 patients). Patient's state was assessed with psychometric scales (Hamilton, Zung, CGI). Enkephalin activity in the blood serum was measured as well. The anxiolytic effects of both drugs were similar but selank had also antiasthenic and psychostimulant effects. The clinical-biological study revealed that patients with GAD and neurasthenia had the decreased level of tau(1/2) leu-enkephalin which was correlated with disease duration, severity of symptoms related to anxiety and asthenia and autonomic disorders...

The effects of Selank, the active component of which is the heptapeptide Thr-Lys-Pro-Arg-Pro-Gly-Pro, which includes the tetrapeptide tuftsin and three natural levorotatory amino acids, on behavior and brain serotonin and noradrenaline levels were studied in adult rats subjected to antenatal hypoxia on days 14-16 of gestation. Administration of Selank (300 microg/kg, i.p.) improved sensory attention levels by factors of 2-3 (p < 0.01), facilitated the learning process by a factor of 1.5 (p < 0.01), normalized the level of investigative activity in the open field and hole board, and restored the balance of activity between the serotoninergic and noradrenergic systems of the brain...

Antiulcer properties of a synthetic anxiolytic Selank and in vivo formed metabolites of this compound were studied on 3 experimental models of ulceration. The test peptides decreased the area of experimental gastric ulcers.

Peptide anxiolytic selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) applied intraperitoneally in doses of 0.01, 0.1, 1.0, and 10.0 mg/kg to mice reduces behavioral manifestations of dopaminergic system induced by apomorphine in the verticalization test. This effect was comparable to that of atypical antipsychotic olanzapine in near-therapeutic doses (0.1 and 1.0 mg/kg, intraperitoneally) and was blocked with nonselective opioid receptor antagonist naloxone (10 mg/kg, intraperitoneally). Radioreceptor assay showed that selank did not displace nonselective D2-dopamine receptor antagonist (3)H-spiperone (EC50>100 microM) and delta- and micro-opioid receptor ligand 3H-DADLE (EC50>40 microM) from specific binding sites on rat brain membranes...

The effects of Selank synthetic analog of Tuftsin, representing the heptapeptide forming Thr-Lys-Pro-Arg-Pro-Gly-Pro, on behavior and serotonin/noradrenalin concentrations in brain were investigated in adult rats exposed to hypoxia during 14-16 days of gestation. It was revealed that injection of Selank (300 mkg/kg, i/p) increased 2--3-fold (p < 0.01) the sensory attention, facilitated 1.5-fold the learning capacity (p < 0.01), normalized exploratory activity in the open field and hole board, and recovered the balance of serotonergic and noradrenergic brain system activity...

We studied the seasonal effects of peptide preparation Selank on orientation and exploratory activity in 36 arctic ground squirrels Citellus undulatus in the open-field and hole-board tests. Selank most significantly increased behavioral activity of hibernating animals in the spring and fall. The test peptide had no effect on locomotor activity of animals. The selective stimulatory effect of Selank on exploratory behavior of hibernating animals was season-dependent. The maximum effect was observed under conditions of seasonal depression-like state...

Biologically active peptides evenly labeled with tritium were used for studying the in vitro and in vivo biodegradation of the peptides. Tritium-labeled peptides with a specific radioactivity of 50-150 Ci/mmol were obtained by high temperature solid phase catalytic isotope exchange (HSCIE) with spillover tritium. The distribution of the isotope label among all amino acid residues of these peptides allows the simultaneous determination of practically all possible products of their enzymatic hydrolysis. The developed analytical method includes extraction of tritium-labeled peptides from organism tissues and chromatographic isolation of individual labeled peptides from the mixture of degradation products...

Experimental and theoretical demonstration of different effect of certain regulatory peptides (RPs) on blood coagulation is available. The problem of the role of RPs in hemostatic processes becomes particularly significant since, first, the peptides are widespread in nature both in animal and plant tissues, second, there is a relationship between the peptide structure and function and, third, both natural and synthetic peptides are used in practical medicine to correct functions of some factors of the hemostatic system...

The effects of the new heptapeptide anxiolytic drug selank (300 mg/kg, i.v.) on the arterial pressure (AP), cerebral blood flow, heart rhythm, respiration, and the AP depression induced by acetylcholine injections was recorded in narcotized male cats. Selank produced a 32 +/- 4.3% decrease in the AP for the first 1-3 min after injection. The drug also induced a 24 +/- 2.8% increase in the cerebral blood flow for the first 5 - 10 min upon injection and then the blood flow was gradually restored on the initial level...

The present concept of relative instability of regulatory peptides (RPs) in organisms must be amended. The recently characterized family of glyprolines and some other prolyl-glycyl-proline (PGP)-containing oligopeptides show the stability quite comparable with those of major pharmacological preparations. The ability of glyprolines to pass gastro-enteric tract barriers opens ways to per-oral administration of this new group of drugs such as semax, selank and their fragments. The most interesting approach is the creation of hybrid ("chimeric") peptide drugs combining the unmodified representatives of various natural RPs that distinctly manifest their inherent physiological activities and cooperate with each other in stabilization of whole peptide in vivo...

The influence of a new heptapeptide Selank on microcirculation in anesthetized white rats was investigated. Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) is a new synthetic anxiolytic which exerts obvious antiulcerogenic action and promotes healing of experimental ulcers. Action of the peptide on gastric blood flow in the stomach by using the method ofhydrogenic clearance and Selank action on mesenteric lymphatic contractility by microscopical observation in situ, were studied. Selank fail to influence basal gastric blood flow but it can normalize blood flow reduced by indomethacin...

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A method of analysis of enkephalinase activity in blood plasma based on the application of Leu-enkephalin generally labeled with tritium at all its amino acid residues was developed. The method allows the simultaneous estimation of activity of several peptidases in microquantities of tissues. [G-3H]Leu-enkephalin was prepared by the method of solid phase catalytic isotope exchange (120 Ci/mmol) and subjected to proteolysis by the treatment with blood plasma. The resulting radioactive metabolites were separated by HPLC in the presence of the mixture of unlabeled fragments of Leu-enkephalin as internal standards...

White laboratory male rats, inbred male C57BL/6 and Balb/c mice, and male Wistar rats, all previously divided on the basis of the type of emotional reactivity, were used to compare the effects of ten peptide compounds of the tuftsin family and Selank on the behavioral manifestations of emotional stress created by a conflict situation. Peptides were shown to have positive emotional effects and antistress actions. Individual physiologically significant effects were seen, due to the molecular structures of the study peptides and/or their degradation fragments...

The actions of the synthetic heptapeptide preparation Selank on learning and memory processes in rats with initially low levels of learning ability were compared with those in normal rats, using a method based on acquisition of a conditioned active avoidance reflex, with repeated administration of peptide 15 min before the start of training sessions for four days. The effects of Selank (300 microg/kg) were compared with the effects of the nootrope piracetam (400 mg/kg). These experiments showed that Selank significantly activated the learning process in rats with initially poor learning ability, with effects apparent after first dose on training day 1...

The action of a synthetic peptide Selank on learning and memory in active avoidance conditioning test was studied in rats with initially low learning ability and normal animals. The peptide was administered repeatedly 15 min prior the training session (4 days). The effect of Selank (300 micrograms/kg) was compared to that of Pyracetam (400 mg/kg). Selank was found to significantly improve learning in rats with low level ability even after a single administration on the first day of training session. The effect progressively increased with repeated Selank treatment: the total numbers of reactions and correct reactions increased, and the number of errors decreased (p < 0...

Comparative study of plasma activities of enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions revealed significant differences between intact BALB/c and C57Bl/6 mice by the half-life of plasma leu-enkephalin. Selank in a dose of 100 micrograms/kg produced an anxiolytic effect in the open-field test and increased the half-life of plasma leu-enkephalin in BALB/c mice, but had no effect on behavioral reactions and enkephalinase activities in C57Bl/6 mice. Our results suggest that anxiolytic activity of Selank is associated with inhibition of enkephalin-degrading enzymes...