Effect Of Semax Research Articles

The effect of semax and the C-terminal peptide PGP on expression of growth factor genes and receptors in rats under conditions of experimental cerebral ischemia

The effect of semax and the C-terminal peptide PGP on expression of growth factor genes and receptors in rats under conditions of experimental cerebral ischemia

The cerebroprotective effects of Semax and Selank in primates at different types of neurosis

The cerebroprotective effects of Semax and Selank in primates at different types of neurosis

Effects of semax and its Pro-Gly-Pro fragment on calcium homeostasis of neurons and their survival under conditions of glutamate toxicity

Semax (100 microM) and its Pro-Gly-Pro fragment (20 and 100 microM) delayed the development of calcium dysregulation and reduction of the mitochondrial potential in cultured cerebellar granule cells under conditions of glutamate neurotoxicity. Incubation with these peptides improved neuronal survival by on average 30%. The neuroprotective effect of semax in cerebral ischemia/hypoxia can be due to improvement of mitochondrial resistance to "calcium" stress.

Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex

Semax had a pronounced neuroprotective and antiamnesic effect during focal photoinduced ischemia of the prefrontal cortex. Intranasal administration of Semax for 6 days decreased the volume of cortical infarction and improved retention and performance of conditioned passive avoidance response.

Semax, an analogue of adrenocorticotropin (4–10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome

Psychostimulants, such as methylphenidate, are currently the most common used drug therapy for children with attention-deficit hyperactivity disorder (ADHD). However, a number of patients with ADHD either fail to respond to these drugs or experience side effects that preclude their use. The heptapeptide Semax is an analogue of the N-terminal fragment (4-10) of adrenocorticotropic hormone, but is completely devoid of any hormonal activity. It has been found to stimulate memory and attention in rodents and humans after intranasal application. Evidence from animal studies revealed that Semax can augment the effects of psychostimulants on central dopamine release and also stimulates central brain-derived neurotrophic factor (BDNF) synthesis. In addition, Semax could improve selective attention and modulate brain development. Since ADHD is likely to be a neurodevelopmental disorder with disturbance in dopamine and BDNF function, it is proposed in this paper that Semax may have good therapeutic potential in ADHD. Furthermore, increased BDNF activity is found to improve Rett syndrome, a severe neurodevelopmental disorder which is, in the majority of cases, caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2). The potential therapeutic effect of Semax in Rett syndrome by increasing central BDNF activity may be of interest for further exploration in animal models of Rett syndrome.

Effect of semax on changes in pain sensitivity and behavior of animals induced by forced swimming

Effect of semax on changes in pain sensitivity and behavior of animals induced by forced swimming

Evenly tritium labeled peptides in study of peptide in vivo and in vitro biodegradation

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. The concentrations of a peptide under study and the products of its biodegradation were calculated from the results of liquid scintillation counting. This approach was used for studying the pathways of biodegradation of the heptapeptide TKPRPGP (Selank) and the tripeptide PGP in blood plasma. The pharmacokinetics of Selank, an anxiolytic peptide, was also studied in brain tissues using the intranasal in vivo administration of this peptide. The concentrations of labeled peptides were determined, and the pentapeptide TKPRP, tripeptide TKP, and dipeptides RP and GP were shown to be the major products of Selank biodegradation. The study of the biodegradation of the heptapeptide MEHFPGP (Semax) in the presence of nerve cells showed that the major products of its biodegradation are the pentapeptide HFPGP and tripeptide PGP. The enkephalinase activity of blood plasma was studied with the use of evenly tritium labeled [Leu]enkephalin. A high inhibitory effect of Semax on blood plasma enkephalinases was shown to arise from its action on aminopeptidases. The method, based on the use of evenly tritium-labeled peptides, allows the determination of peptide concentrations and the activity of enzymes involved in their degradation on a μg scale of biological samples both in vitro and in vivo.

Effects of semax against the background of dopaminergic receptor blockade with haloperidol

We studied the neurotropic effects of ACTH(4-10) analog semax against the background of dopaminergic receptors blockade with haloperidol. Intranasal administration of semax (0.05, 0.2, and 0.6 mg/kg) produced virtually no effect on disturbances of orientation and exploratory reactions and motor activity caused by intraperitoneal injection of 0.2 mg/kg haloperidol. By contrast, preliminary administration of 0.05 mg/kg semax prevented haloperidol-induced disturbances in active avoidance conditioning.

Semax, An ACTH(4-10) Analogue with Nootropic Properties, Activates Dopaminergic and Serotoninergic Brain Systems in Rodents

Corticotrophin (ACTH) and its analogues, particularly Semax (Met-Glu-His-Phe-Pro-Gly-Pro), demonstrate nootropic activity. Close functional and anatomical links have been established between melanocortinergic and monoaminergic brain systems. The aim of present work was to investigate the effects of Semax on neurochemical parameters of dopaminergic- and serotonergic systems in rodents. The tissue content of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum was significantly increased (+25%) 2 h after Semax administration. The extracellular striatal level of 5-HIAA gradually increased up to 180% within 1-4 h after Semax (0.15 mg/kg, ip) administration. This peptide alone failed to alter the tissue and extracellular concentrations of dopamine and its metabolites. Semax injected 20 min prior D: -amphetamine dramatically enhanced the effects of the latter on the extracellular level of dopamine and on the locomotor activity of animals. Our results reveal the positive modulatory effect of Semax on the striatal serotonergic system and the ability of Semax to enhance both the striatal release of dopamine and locomotor behavior elicited by D-amphetamine.

C-Terminal Pro-Gly-Pro Tripeptide in Contrast to Full-Length Neuropeptide Semax Exhibits No Neuroprotective Effect in Experimental Cerebral Ischemia

The C-terminal fragment Pro-Gly-Pro of semax does not modulate the development of symptoms of neurological deficiency and mortality in rats with incomplete global cerebral ischemia. Hence, previously revealed neuroprotective effects of semax are mainly determined by corticotropin ACTH4-7 fragment.

P.5.013 Study of neurotropic effects ofSemax analogues depending on their structure

P.5.013 Study of neurotropic effects ofSemax analogues depending on their structure

Effects of Semax on dopaminergic and serotoninergic systems of the brain.

Effects of Semax on dopaminergic and serotoninergic systems of the brain.

Effect of Semax peptide on survival of cultured rat pheochromocytoma cells during oxidative stress.

We studied the effects of Semax (antiinsulin peptide with neuroprotective effect) on the survival of cultured rat pheochromocytoma cell after oxidative stress induced by short-term incubation with hydrogen peroxide. Studies with fluorescent dyes propidium iodide and Hoechst 33258 showed that cell incubation with hydrogen peroxide led to the formation of damaged cells with characteristic signs of necrosis. Semax dose-dependently reduced the number of cells damaged by oxidative stress. The efficiency of Semax depended on the time of its addition to the culture medium. The results suggest that the neuroprotective effect of Semax in ischemic stroke can be due to its capacity to protect neurons from damage caused by oxidative stress.

The effect of semax on animal pain sensitivity in various experimental models.

The effect of semax on animal pain sensitivity in various experimental models.

Trophic effects of nootropic peptide preparations cerebrolysin and semax on cultured rat pheochromocytoma.

Trophic characteristics of neuroprotectors cerebrolysin and semax were evaluated by their capacity to induce differentiation and improve survival of cultured rat pheochromocytoma (PC12) cells. Morphological signs of cell differentiation (enlargement and formation of processes) were seen 24 h after addition of cerebrolysin into culture medium. Cerebrolysin improved survival of PC12 cells in serum-free medium. In a concentration of 100 microg/ml cerebrolysin decreased the content of apoptotic cells from 32% (control) to 10%. Semax produced no trophic effect on PC12 cells. hence, the neuroprotective effect of cerebrolysin in vivo probably results from trophic activity, while the protective effects of semax are mediated by other mechanisms.

Semax and selank inhibit the enkephalin-degrading enzymes from human serum]

A dose-dependent effect of synthetic heptapeptides Semax (Met-Glu-His-Phe-Pro-Gly-Pro) and Selank (Thr-Lys-Pro-Arg-Pro-Gly-Pro) on the enkephalin-degrading enzymes of human serum was demonstrated. The inhibitory effects of Semax (IC50 10 microM) and Selank (IC50 20 microM) are more pronounced than those of puromycin (IC50 10 mM), bacitracin, and some other inhibitors of peptidases. Beside the heptapeptides, their pentapeptide fragments also possessed an inhibitory effect; tri-, tetra-, and hexapeptide fragments did not display such an effect. As the above enzymes take part in degradation of not only enkephalins but also other regulatory peptides, it can be assumed that one of the mechanisms of biological activity of Semax and Selank is related to this inhibitory activity of theirs.

Effects of Semax, a peptide ACTH4-10 analogue, on the respiratory burst in human neutrophils.

Effects of Semax, a peptide ACTH4-10 analogue, on the respiratory burst in human neutrophils.

Effect of semax on homeostasis of gastric mucosa in albino rats

Effect of semax on homeostasis of gastric mucosa in albino rats

Effect of Semax on homeostasis of gastric mucosa in albino rats.

The ACTH(4-7)analogue Semax administered intraperitoneally in a dose of 50 microg/kg 1 h before exposure to ulcerogenic factors (ethanol, water immersion immobilization stress) protected gastric mucosa from damage. Postoperative treatment with Semax for 5 days after application of glacial acetic acid on the mucosa prevented acetic acid-induced ulcers and promoted their healing. The antiulcer effects of Semax in the studied dose were comparable with those of tripeptide Pro-Gly-Pro in a dose of 1 mg/kg.

Effect of semax and ACTH (5–10) on electrical activity of central neurons

Experiments on cats with the use of microelectrode technique and microionophoresis show that semax and ACTH(5–10) modulate spontaneous activity of approximately 60% cortical neurons, which probably accounts for their effect on general integrative function of the cortex. Neurons of the medial vestibular nucleus are highly sensitive to microionophoretic applications of these peptides (59–69% cells). It is assumed that the direct effect of semax and ACTH(5–10) to a great extent determines their efficiency in motion sickness.