Semax - Educational materials

Semax, also known as SEMAX heptapeptide (MEHFPGP), is a synthetic peptide drug developed from the molecular structure of adrenocorticotropic hormone (ACTH). This peptide has been shown to have pronounced nootropic, neuroprotective and neurotrophic properties. It can significantly improve learning and memory, and help counteract anxiety and depression. Semax is one of the rare regulatory peptide analogs that has gone all the way from basic research to practical application. 

Semax has undergone extensive research in Russia and has been approved by the government of the Russian Federation for the treatment of stroke, transient ischemic attack, memory and cognitive disorders, ulcer disease, optic nerve disease and immune system enhancement. This comprehensive article will discuss Semax peptide's structure, mechanism of action, dosage, side effects, research citations, case reports and recommendations for potential applications.

Context and structure of the Semax peptide

Semax is a modified version of a naturally occurring neuropeptide called ACTH (adrenocorticotropic hormone). It was developed in Russia in the 1980s for the TREATMENT of stroke and other brain injuries, but has since been shown to have a wide range of potential therapeutic uses.

Hemptapeptide Semax (MEHFPGP) consists of a sequence of seven amino acids: Met-Glu-His-Phe-Pro-Gly-Pro. ACTH is modified by replacing Proline at the second position with its D-form isomer and adding a small synthetic tripeptide (Lys-Pro-Val) at the N-terminus. These modifications improve the stability and bioavailability of Semax, allowing it to better penetrate the blood-brain barrier and affect the brain.

Semax's peptide skeleton is similar to that of other neuropeptides, consisting of a linear chain of amino acids linked together by peptide bonds. Its three-dimensional structure is characterized by its helical shape, which allows it to interact with specific receptors in the brain. 

SEMAX benefits: what you need to know

As a synthetic analog of adrenocorticotropic hormone 4-10, Semax has been found in scientific studies to have nootropic effects and neuroprotective activity. 

• • Studies have suggested the administration of Semax peptide for the treatment of CNS diseases such as ischemic stroke, dyscerebral encephalopathy and optic nerve atrophy, as well as to enhance adaptive abilities under extreme conditions.

• • Semax has been shown to improve learning and memory, reduce anxiety, improve attention and short-term memory, help during recovery from stroke/dysfunction, improve glaucoma optic neuropathy, act as an analgesic and help treat ADHD. 

• • Studies also suggest that Semax may have neuroprotective effects, making it a promising candidate for treating neurodegenerative diseases such as Alzheimer's and Parkinson's.

• • In addition, Semax has been found to strengthen the immune system and improve physical endurance.

• • In addition, Semax's neuroprotective effects may help protect the brain from various types of stress and damage. 

• • Semax has been extensively studied in Russia and approved by the government of the Russian Federation for various medical uses, including the treatment of stroke, transient ischemic attack, memory, cognitive disorders, ulcer disease, optic nerve disease and strengthening the immune system.

How SEMAX works: An explanation of its possible mechanism of action     

Semax has been shown to bind to receptors for the neuropeptides ACTH and alpha-MSH (melanocyte-stimulating hormone), as well as to a specific receptor for Semax itself, called the low-affinity NGF receptor. This interaction with specific receptors triggers a cascade of biochemical events within neurons, enhancing cognitive function and other beneficial effects observed with Semax administration.

Another possible mechanism of action of Semax involves activation of dopaminergic and serotonergic brain systems, as demonstrated in rodents. Researchers report that Semax has a positive modulatory effect on the serotonergic system in the striatum, as evidenced by an increase in the tissue content of the metabolite 5-hydroxyindoleacetic acid (5-HIAA). The peptide also increased extracellular striatal levels of the 5-HIAA metabolite in rodents. In addition, Semax has the ability to increase both dopamine release and locomotor behavior by interacting with the dopaminergic system [1].

In stroke, Semax has been shown to increase plasma BDNF levels, improve motor function and accelerate functional recovery in ischemic stroke patients. It enhances the immune response and alters the expression of genes related to the immune and vascular systems, suggesting that its neuroprotective mechanism works through neuroimmune transmission. In addition, Semax exhibits anti-inflammatory properties and may reduce the expression of pro-inflammatory genes induced by ischemia. It also modulates processes related to inflammation, cell death, neuroprotection and regeneration during cerebral ischemia, indicating its potential neuroprotective properties [5-10]. 

Semax was found to increase BDNF protein levels and tyrosine phosphorylation of trkB in the hippocampal region. This modulation of the hippocampal BDNF/trkB system has been suggested as the mechanism by which Semax affects brain cognitive function [6].Attention: Along with scientific studies, other proposed mechanisms are discussed.

SEMAX dosage: based on scientific research?

The appropriate doses of Semax in research studies depend on the condition, route of administration and duration of treatment. In studies of anxiety and depression, Semax was administered intranasally at doses of 50 and 500 μg/kg, 15 minutes before the study. Some studies have also used lower doses of Semax, such as 1% and 0.1% solutions [3-6].

Different doses and courses of treatment have been used in post-stroke patients. The most effective daily doses were found to be 12 mg for patients with moderate stroke and 18 mg for patients with severe stroke, administered over 5-10 days. Another study used a high dose of 100 mg/kg Semax and an equivalent concentration of PGP tripeptide of 37.5 mg/kg, administered intraperitoneally at different intervals after stroke [6-11].

Semax has also been studied for its potential use in palliative therapy for motor neuron disease, where patients received a daily dose of 12 mg intranasally over two 10-day periods with a 2-week break in between [11].

In animal studies, doses of Semax ranged from 0.05 to 450 μg/kg, administered intranasally or intraperitoneally. Semax showed potential in preventing stress-induced ulcers at a dose of 50 μg/kg administered intraperitoneally. In the myocardial infarction study, Semax was administered intraperitoneally at a high dose of 150 μg/kg at various intervals after occlusion [13-15, 20-29, 31-42].

In general, the dose of Semax peptide used in research studies varies widely depending on the condition being treated and the route of administration. Both low and high doses have been used, and Semax has shown potential in a number of conditions, making it an interesting area for further research.

Note: For more information on dosage, read the full article.

Side effects of SEMAX: what to watch out for

Side effects of Semax, if they occur, can be compared to drinking too strong a cup of coffee; common side effects of Semax include mild headaches, nausea and nasal irritation. In rare cases, increased anxiety or insomnia may occur.

Scientific research on Semax peptide

Semax peptide versus anxiety and depression: is it effective?

Semax is a heptapeptide with nootropic and neuroprotective properties. In a study involving rats, it was found that early-life exposure to the antidepressant drug fluvoxamine caused long-term impairments in anxiety behavior, learning ability and brain monoamine content. However, administration of Semax mitigated these effects by reducing anxiety behaviors, improving learning ability and normalizing brain levels of biogenic amines that had been disrupted by fluvoxamine exposure. The study showed that Semax has potential as an antidepressant and anti-anxiety agent, with the ability to prevent behavioral deficits caused by abnormal serotonin levels [2].

Another study in rats examined the effects of Semax (MEHFPGP) on anxiety and depression. The results indicated that Semax at doses of 50 and 500 microg/kg showed anti-anxiety and antidepressant effects in rats with elevated anxiety and depression induced by tetragastrin (CCK-4) administration. As for the dosage, the group received Semax at doses of 50 and 500 microg/kg intranasally 15 minutes before testing for anxiety and depression [3].

The effects of Semax, an ACTH analog (4-10), were studied in rats with MPTP-induced brain dopamine system disorders. MPTP administration resulted in decreased locomotor activity and increased anxiety, while Semax administration alleviated these behavioral changes. The protective effect of Semax is due to its modulatory effect on the brain dopamine system and neuroprotective properties [4].

Benefits of Semax peptide in stroke treatment

The controlled study was designed to evaluate the effects of Semax and rehabilitation time on plasma BDNF levels and motor performance in ischemic stroke patients. The results showed that the administration of Semax increased plasma BDNF levels, improved motor performance and accelerated functional recovery, regardless of rehabilitation time. Early rehabilitation and administration of Semax positively correlate with improved motor function in patients after ischemic stroke. Regarding dosage, the standard Semax administration regimen used in the study consisted of two stages lasting 10 days with a 20-day interval. The dose used was 6000 μg/day [5].

In another study in 30 patients with acute ischemic stroke, Semax was shown to improve the rate of recovery of neurological function, especially motor impairment. The study found that the most effective daily doses of Semax were 12 mg for patients with moderate strokes and 18 mg for patients with severe strokes. The course of treatment for both doses was 5 and 10 days, respectively [6].

A study in rats with focal cerebral ischemia showed that Semax significantly enhanced the immune response by affecting various signaling pathways and biological processes. The study suggested that Semax's neuroprotective mechanism works through neuroimmune penetration. The study used a dose of 100 μg/kg bw of Semax and an equivalent concentration of 37.5 μg/kg of PGP tripeptide. Intraperitoneal injections of Semax, PGP or saline were administered 15 minutes, 1 hour, 4 hours and 8 hours after permanent middle cerebral artery occlusion. The first injection was given at 15 minutes after the procedure to closely simulate the clinical use of Semax, as studies have shown that the efficacy of Semax treatment increases when the time between occlusion and the first injection in stroke patients decreases [7].

Semax primarily enhanced genes related to the immune and vascular systems in rat brain tissue. The results revealed that Semax alters the expression of genes that modulate the number and mobility of immune cells. It also increases the expression of genes encoding chemokines and immunoglobulins. The immunomodulatory effect of Semax is likely the key mechanism underlying its neuroprotective effects [8].

In another study, Semax was found to reduce the expression of several pro-inflammatory genes induced by ischemia. These results suggested that the protective effect of Semax in stroke may be due to its anti-inflammatory properties [9].

In an animal study, Semax was shown to suppress the expression of inflammatory genes, downregulate proteins associated with cell death, and activate proteins associated with neuroprotection and recovery during brain ischemia. These results suggested that Semax may exhibit neuroprotective properties by modulating these processes at the transcriptome and protein level [10].

Brain benefits of Semax peptide

Semax and motor neuron disease (MND)

The study was conducted on 27 patients with motor neuron disease (MND). The researcher evaluated the effect of Semax on chronic partial denervation (CPD) and quality of life. It was found that Semax significantly improved total quality of life estimates due to improvements in emotional state and motivation in MND patients with a maximum effect on day 10. In terms of dose, patients received Semax (1% solution) intranasally in two 10-day periods with a 2-week break in between, at a daily dose of 12 mg. This suggests that a daily dose of 12 mg of Semax in two 10-day okeras with a 2-week break between them could be viable for palliative therapy of MND [11].

Semax and neurodegenerative diseases

Alzheimer's disease is characterized by amyloid-β (Aβ) protein aggregation, modulated by metal ions and phospholipid membranes, particularly Cu2+ ions. An in-vitro study showed that Semax inhibited fibril formation by interfering with fibrillogenesis of Aβ: Cu2+ complexes. Semax was found to prevent the formation of Aβ:Cu2+ complexes and exhibit anti-aggregation and protective properties, especially in the presence of Cu2+. These results suggest that Semax has potential as a multifunctional compound for the treatment of Alzheimer's disease [12].

Forebrain basal cholinergic neurons degenerate during Alzheimer's progression. Another in-vitro study investigated the effect of Semax on the survival of forebrain basal cholinergic neurons. The study found that Semax increased the survival of cholinergic neurons by about 1.5-1.7 times and stimulated choline acetyltransferase activity. The results suggest that Semax may be a promising compound for treating Alzheimer's-related dementia. In experiments, Semax was used in a concentration range of 1 nM to 10 microM [13].

Semax and brain dysfunction 

An animal study examined the effects of Semax on the psychomotor development of rats exposed to fetal valproic acid (VA) syndrome, a condition associated with autism spectrum disorders. The results showed that Semax partially normalized the psychomotor development of the young rats, reduced their levels of depression, normalized their nociception and increased their desire for new social experiences. The study also concluded that Semax showed positive modulatory and protective effects on the developing brain, including in cases of neonatal-induced dysfunction. The study suggested that Semax may correct brain dysfunction caused by prenatal neurotoxic effects and may have a protective effect against neurodegenerative diseases. As for the dose, the researcher used Semax intranasally in animals at a dose of 0.05 mg/kg [14].

Semax and brain damage

An animal study examined the effects of Semax on behavior and changes in the brain's dopaminergic system induced by the MPTP neurotoxin. The neurotoxin decreased motor activity and increased anxiety, while daily intranasal administration of Semax reduced the severity of these disorders. The protective effect of Semax may be due to its modulatory effect on the dopaminergic system and neurotrophic effects. Semax was administered intranasally at a dose of 0.2 mg/kg [15].

Semax as a nootropic peptide

Semax and cognitive effects

In a study in rats, Semax was found to increase BDNF protein levels and trkB tyrosine phosphorylation levels in the hippocampal region, enhancing conditioned avoidance responses. Researchers suggested that Semax promotes brain cognitive function by modulating the expression and activation of the hippocampal BDNF/trkB system [16].

Semax and learning and memory formation

Semax shows significant neuroprotective effects and improves learning and memory formation. Recent studies have shown that Semax binds specifically to the base of the forebrain with a dissociation constant of 2.4+/-1.0 nm, increasing BDNF levels in this region but not in the cerebellum. These results suggest that the cognitive effects of Semax may be related to increased BDNF protein levels in the forebrain and that specific Semax binding sites are present in this brain region [17].

Another study showed that Semax effectively counteracted heavy metal-induced inhibition of learning and memory in rats, as did ascorbic acid. It has been suggested that the antioxidant potential of Semax is responsible for this significant protective effect [18].

Intranasal administration of Semax for six consecutive days in rats produced significant antimuscarinic and neuroprotective effects. This was demonstrated by reducing the extent of cortical tissue damage and increasing the ability to behave and perform conditioned passive avoidance behavior [19].

Semax reduced neurological deficits and increased survival in rats with model cerebral ischemia. The study showed that Semax reduced neurological deficits and amnesia in a gradual passive avoidance situation when it was administered preventively in rats with model cerebral ischemia. The dose of Semax used in this study ranged from 0.3 to 1.2 mg/kg per day [20].

Another study showed that Semax was able to prevent retrograde amnesia in mice under stressful conditions and improve their survival in the altitude testing chamber [21].

Thrombosis-induced ischemic infarcts in the prefrontal cortex of rats were found to impair spatial memory. However, chronic intranasal administration of Semax at a dose of 250 microg/kg/day for six days after thrombolysis led to recovery of the animals' learning ability. The peptide's neuroprotective activity and ability to stimulate the synthesis of neurotrophic factors may explain its long-term anti-amnestic effects [22].

Nootropic and analgesic effects of Semax preparation

One study examined the effects of Semax on learning and pain sensitivity in rats through intraperitoneal and intranasal administration. Semax showed nootropic and analgesic activity after intraperitoneal administration. A stronger learning enhancement effect was observed after intranasal administration. Intranasal administration, however, had no effect on pain sensitivity. The researchers suggested that Semax may have different mechanisms and brain structures involved in its nootropic and analgesic effects [36].

Semax peptide versus ADHD: what research says

One study reported that Semax heptapeptide improves memory, attention and central dopamine release in rodents. It also stimulates the synthesis of brain-derived neurotrophic factor (BDNF) and may improve selective attention and modulate brain development. Therefore, Semax may have therapeutic potential in ADHD, a neurodevelopmental disorder characterized by dopamine and BDNF dysfunction. Additionally, Semax may ameliorate Rett syndrome, a severe neurodevelopmental disorder, by increasing central BDNF activity. Further extensive studies are needed to investigate this potential therapeutic effect in the management of ADHD and Rett syndrome [23].

Semax and integrity of the gastrointestinal tract

Improving the gut microbiota

In one study, Semax was shown to affect the gut microbiota of rats subjected to chronic restraint stress. Chronic stress exposure caused a decrease in obligate bacteria in rats, but an increase in opportunistic microorganisms. However, Semax at doses of 50 and 150 μg/kg prevented these stress-induced changes and maintained a healthy balance of the microbiota. The researchers proposed that Semax's effect could be attributed to its central neurotropic effects and its ability to bind to peripheral melanocortin receptors located in the gut. In terms of dosage, Semax was administered to male Wistar rats intraperitoneally at doses of 5, 50, 150 and 450 μg/kg, 12-15 minutes before exposure to stress [24].

Protecting the integrity of the large intestine

Stress causes various negative changes in the colon, including atrophy, inflammation, changes in mast cell activity and increased corticosterone levels. However, in an animal study, administration of Semax peptide reduced corticosterone levels, reduced pathomorphological changes and helped the colon adapt to stress. The positive effects of the peptide can be attributed to its various physiological and pharmacological effects. The group received Semax at doses of 5, 50, 150 and 450 μg/kg, 12-15 minutes before exposure to restraint stress [25].

Semax and peptic ulcer disease

In one study, the Semax peptide significantly promoted ulcer healing in patients with refractory peptic ulcer disease when combined with traditional preparations. On day 14 of treatment, 89.5% of patients receiving Semax intranasally had healed ulcers compared to 30.8% in the control group. Further clinical trials are needed to evaluate the anti-ulcer activity of Semax in various combinations with conventional anti-ulcer drugs [26].

Another study in rats with indomethacin-induced ulcers showed that intraperitoneal administration of Semax at a dose of 50 mg/kg prevented indomethacin-induced reduction in blood flow. It was concluded that the potential anti-ulcer effect of Semax may be related to improved blood flow in the gastric wall impaired by indomethacin [27].

Another study tested the effects of the peptides gliprolin and Semax on ulcers in rats. The peptides accelerated the ulcer healing process, with Semax being the most effective. The peptides were also shown to reduce inflammation in the ulcer zone. Their anti-ulcer effect was attributed to their ability to accelerate ulcer clarification and activate the process of healing and epithelialization [28].

Another study showed that Semax at a dose of 50 μg/kg protected the gastric mucosa from damage caused by ulcerative agents such as ethanol and stress. In addition, postoperative treatment with Semax prevented the formation of acetic acid-induced ulcers and promoted their healing. The anti-ulcer effect of Semax was similar to that of PGP tripeptide at the dose tested. The dose of Semax used in the study was 50 μg/kg administered intraperitoneally [29].

Semax and cerebrovascular insufficiency

One study tested the effects of Semax in 187 patients with cerebrovascular insufficiency (CI). Patients were evaluated for tolerability, efficacy and complications of Semax administration. Administration of Semax resulted in significant clinical improvement, stabilization of disease progression, and reduced the risk of stroke and transient ischemic attacks. It was well tolerated by patients, including those in older age groups, and had a low incidence of adverse effects [30].

Semax vs. acute myocardial infarction

In a study in rats with acute myocardial infarction (AMI), Semax prevented ischemia-induced ultrastructural changes in cardiomyocytes. It also reduced the increase in plasma nitrate concentrations without affecting cardiac function. The researchers suggested that Semax may have a protective effect on the heart in AMI. In the study, Semax (150 μg/kg) was administered intraperitoneally at 15 minutes and 2 hours after coronary occlusion [31].

In another study, administration of Semax after coronary artery occlusion prevented changes in cardiomyocyte structure and reduced plasma nitrate levels in rats. For 28 days, after myocardial infarction, Semax partially prevented an increase in left ventricular end-diastolic pressure and improved cardiomyocyte hypertrophy. In addition, it improved the excessive growth of the contractile and mitochondrial apparatus. These results indicated that Semax had a positive effect on the development of heart failure and left ventricular remodeling, even at later stages after myocardial infarction. The dose of Semax used in this study was 150 μg/kg body weight. Semax was administered intraperitoneally twice on the day of left descending coronary artery occlusion, 15 minutes and 2 hours after the occlusion, and once daily for the next 6 days [32].

Activation of the sympathetic nervous system worsens the course of myocardial infarction. A study showed that Semax peptide reduced sympathetic nervous system activation. It also prevented an increase in the density of sympathetic endings in rats with myocardial infarction. The peptide also reduced α-adrenoreceptor density and vascular reactivity in the tail artery of rats after ischemia-reperfusion injury [33].

Semax and optic nerve disease

In one study, three groups of patients received Semax by different routes, with group 1 receiving nasal drops, group 2 receiving endonasal electrophoresis, and group 3 being the control group. The addition of Semax to the treatment of optic nerve disease improved visual function, increased the speed of recovery and protected nerve tissue from the consequences of injury. Positive changes in the clinical picture were observed, including improved visual acuity, expansion of the total visual field, optic nerve conduction, increased electrical sensitivity and improved color vision [34].

Semax and optic neuropathy

Neuroprotective therapy for patients with glaucoma, including the peptide Semax, was more effective than traditional neuroprotective treatment. In one study, Semax showed benefit due to its pathogenic activity with neuroprotective and neurotrophic effects [35].

Semax a pain

One study examined the effects of ACTH4-10 and its analog Semax on pain sensitivity in various animal models. ACTH4-10 showed analgesic effects at a dose of 0.5 mg/kg, while lower doses had no effect. Semax showed a dose-dependent reduction in pain sensitivity in all experimental models, indicating that replacing the three C-terminal amino acid residues in ACTH4-10 with the Pro-Gly-Pro sequence increased its analgesic potency after peripheral injection. The study administered ACTH4-10 at a dose of 0.5 mg/kg and Semax at doses ranging from 0.015 to 0.500 mg/kg [37].

Semax vs. diurnal rhythm

A study in rats found that the nootropic preparation Semax normalized their circadian locomotor rhythm. This effect was evident by increasing the amplitude, shifting the acrophase and changing the spectral characteristics. In addition, the preparation decreased the integral chronobiological index. According to the study, the specific effect of this cognitive enhancer may be its ability to synchronize rhythms and regulate heart rate [38].

Semax versus immunomodulation

An animal study investigated the immune corrective effects of Semax on the "social" stress-induced immune response. The results showed that Semax effectively restored cellular and humoral immunogenic responses and neutrophil phagocytic activity, indicating its potential as an immune corrector with immunomodulatory properties. Further research in this area is needed [39].

Another study examined the effects of Semax on the cellular composition of splenic lymphoid structures in rats subjected to various stress conditions. When evaluating recovery from stress, Semax reduced stress-induced macrophage proliferation and destructive processes in the spleen. The results indicated Semax's ability to mitigate the adverse effects of stress on this important organ [40].

Semax versus pancreatitis

An animal study compared the effects of Semax with drugs on acute pancreatitis. The results showed that a single administration of Semax reduced animal loss, hyperfermentation and activation of lipid peroxidation. It also improved microcirculation and facilitated healing without significant fibrotic changes in the parenchyma. Semax was found to be more effective than drugs [41].

In another study, Semax was found to positively affect ultrastructural changes in rats with acute pancreatitis. When administered at a dose of 0.1 mg/kg through the pancreatic duct, Semax prevented increased necrosis of acinar tissues and inhibited suppurative inflammation. These effects led to the induction of sclerosis and atrophy, ultimately preserving significant areas of the pancreas [42].

Summary

Semax is a synthetic peptide drug that has undergone extensive research in Russia and has shown promising results in treating various conditions such as cognitive ailments, stroke, ulcer disease and optic nerve disease. It is believed to have nootropic, neuroprotective and neurotrophic properties that can enhance memory and learning, reduce anxiety, improve attention and short-term memory, and provide analgesic effects. What's more, Semax is also known to boost the immune system, making it a hopeful treatment for many conditions. Besides, recent studies propose that Semax may also provide neuroprotective benefits and be an effective therapy for treating neurodegenerative diseases such as Alzheimer's disease. Semax carries significant potential in a variety of medical fields, and further research is crucial to fully understand its action and potential applications.

Disclaimer

This article was written for educational purposes and is intended to raise awareness of the substance being discussed. It is important to note that the substance discussed is a substance, not a specific product. The information contained in the text is based on available scientific research and is not intended to serve as medical advice or promote self-medication. The reader should consult any health and treatment decisions with a qualified health professional.

Sources

1. 1. Eremin, K. O., Kudrin, V. S., Saransaari, P., Oja, S. S., Grivennikov, I. A., Myasoedov, N. F., & Rayevsky, K. S. (2005). Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochemical research, 30(12), 1493-1500. https://doi.org/10.1007/s11064-005-8826-8 https://pubmed.ncbi.nlm.nih.gov/16362768/ 

1. 1. Glazova, N. Y., Manchenko, D. M., Volodina, M. A., Merchieva, S. A., Andreeva, L. A., Kudrin, V. S., Myasoedov, N. F., & Levitskaya, N. G. (2021). Semax, synthetic ACTH(4-10) analogue, attenuates behavioral and neurochemical alterations following early-life fluvoxamine exposure in white rats. Neuropeptides, 86, 102114. https://doi.org/10.1016/j.npep.2020.102114 https://pubmed.ncbi.nlm.nih.gov/33418449/ 

1. 1. Levitskaia, N. G., Vilenskiĭ, D. A., Sebentsova, E. A., Anreeva, L. A., Kamenskiĭ, A. A., & Miasoedov, N. F. (2010). Izvestiia Akademii nauk. Seriia biologicheskaia, (2), 231-237. https://pubmed.ncbi.nlm.nih.gov/20387390/ 

1. 1. Levitskaia, N. G., Sebentsova, E. A., Andreeva, L. A., Alfeeva, L. I.u, Kamenskiĭ, A. A., & Miasoedov, N. F. (2002). Neĭroprotektornye éffekty semaksa na fone MFTP-vyzvannykh narusheniĭ dofaminergicheskoĭ sistemy mozga [Neuroprotective effects of semax in MPTP-induced disturbances of brain dopamine system]. Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova, 88(11), 1369-1377. https://pubmed.ncbi.nlm.nih.gov/12587264/ 

1. 1. Gusev, E. I., Martynov, M. Y., Kostenko, E. V., Petrova, L. V., & Bobyreva, S. N. (2018). Éffektivnost' semaksa pri lechenii bol'nykh na raznykh stadiiakh ishemicheskogo insul'ta [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 118(3. Vyp. 2), 61-68. https://doi.org/10.17116/jnevro20181183261-68 https://pubmed.ncbi.nlm.nih.gov/29798983/ 

1. 1. Gusev, E. I., Skvortsova, V. I., Miasoedov, N. F., Nezavibat'ko, V. N., Zhuravleva, E. I.u, & Vanichkin, A. V. (1997). Effektivnost' semaksa v ostrom periode polusharnogo ishemicheskogo insul'ta (klinicheskoe i élektrofiziologicheskoe issledovanie) [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 97(6), 26-34. https://pubmed.ncbi.nlm.nih.gov/11517472/ 

1. 1. Medvedeva, E. V., Dmitrieva, V. G., Limborska, S. A., Myasoedov, N. F., & Dergunova, L. V. (2017). Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats. Molecular genetics and genomics : MGG, 292(3), 635-653. https://doi.org/10.1007/s00438-017-1297-1 https://pubmed.ncbi.nlm.nih.gov/28255762/

1. 1. Medvedeva, E. V., Dmitrieva, V. G., Povarova, O. V., Limborska, S. A., Skvortsova, V. I., Myasoedov, N. F., & Dergunova, L. V.. (2014). The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis. BMC genomics, 15, 228. https://doi.org/10.1186/1471-2164-15-228 https://pubmed.ncbi.nlm.nih.gov/24661604/ 

1. 1. Dergunova, L. V., Dmitrieva, V. G., Filippenkov, I. B., Stavchansky, V. V., Denisova, A. E., Yuzhakov, V. V., Sevan'kaeva, L. E., Valieva, L. V., Sudarkina, O. Y., Gubsky, L. V., Myasoedov, N. F., & Limborska, S. A. (2021). Molekuliarnaia biologiia, 55(3), 402-411. https://doi.org/10.31857/S0026898421010043 https://pubmed.ncbi.nlm.nih.gov/34097675/ 

1. 1. Sudarkina, O. Y., Filippenkov, I. B., Stavchansky, V. V., Denisova, A. E., Yuzhakov, V. V., Sevan'kaeva, L. E., Valieva, L. V., Remizova, J. A., Dmitrieva, V. G., Gubsky, L. V., Myasoedov, N. F., Limborska, S. A., & Dergunova, L. V.. (2021). Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion. International journal of molecular sciences, 22(12), 6179. https://doi.org/10.3390/ijms22126179 https://pubmed.ncbi.nlm.nih.gov/34201112/ 

1. 1. Serdiuk, A. V., Levitskiĭ, G. N., Miasoedov, N. F., & Skvortsova, V. I. (2007). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 107(4), 29-39. https://pubmed.ncbi.nlm.nih.gov/18379501/ 

1. 1. Sciacca, M. F. M., Naletova, I., Giuffrida, M. L., & Attanasio, F. (2022). Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models. ACS chemical neuroscience, 13(4), 486-496. https://doi.org/10.1021/acschemneuro.1c00707 https://pubmed.ncbi.nlm.nih.gov/35080861/ 

1. 1. Grivennikov, I. A., Dolotov, O. V., Zolotarev, Y. A., Andreeva, L. A., Myasoedov, N. F., Leacher, L., Black, I. B., & Dreyfus, C. F. (2008). Effects of behaviorally active ACTH (4-10) analogue - Semax on rat basal forebrain cholinergic neurons. Restorative neurology and neuroscience, 26(1), 35-43. https://pubmed.ncbi.nlm.nih.gov/18431004/

1. 1. Malyshev, A. V., Razumkina, E. V., Dubynin, V. A., & Myasoedov, N. F. (2013). Semax corrects brain dysfunction caused by prenatal introduction of valproic acid. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections, 450, 126-129. https://doi.org/10.1134/S0012496613030046 https://pubmed.ncbi.nlm.nih.gov/23821048/ 

1. 1. Levitskaya, N. G., Sebentsova, E. A., Andreeva, L. A., Alfeeva, L. Y., Kamenskii, A. A., & Myasoedov, N. F. (2004). The neuroprotective effects of Semax in conditions of MPTP-induced lesions of the brain dopaminergic system. Neuroscience and behavioral physiology, 34(4), 399-405. https://doi.org/10.1023/b:neab.0000018752.59465.28 https://pubmed.ncbi.nlm.nih.gov/15341218/ 

1. 1. Dolotov, O. V., Karpenko, E. A., Inozemtseva, L. S., Seredenina, T. S., Levitskaya, N. G., Rozyczka, J., Dubynina, E. V., Novosadova, E. V., Andreeva, L. A., Alfeeva, L. Y., Kamensky, A. A., Grivennikov, I. A., Myasoedov, N. F., & Engele, J. (2006). Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain research, 1117(1), 54-60. https://doi.org/10.1016/j.brainres.2006.07.108 https://pubmed.ncbi.nlm.nih.gov/16996037/ 

1. 1. Dolotov, O. V., Karpenko, E. A., Seredenina, T. S., Inozemtseva, L. S., Levitskaya, N. G., Zolotarev, Y. A., Kamensky, A. A., Grivennikov, I. A., Engele, J., & Myasoedov, N. F. (2006). Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. Journal of neurochemistry, 97 Suppl 1, 82-86. https://doi.org/10.1111/j.1471-4159.2006.03658.x https://pubmed.ncbi.nlm.nih.gov/16635254/ 

1. 1. Inozemtsev, A. N., Bokieva, S. B., Karpukhina, O. V., Gumargalieva, K. Z., Kamensky, A. A., & Myasoedov, N. F. (2016). Semax prevents learning and memory inhibition by heavy metals. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections, 468(1), 112-114. https://doi.org/10.1134/S0012496616030066 https://pubmed.ncbi.nlm.nih.gov/27411820/ 

1. 1. Romanova, G. A., Silachev, D. N., Shakova, F. M., Kvashennikova, Y. N., Viktorov, I. V., Shram, S. I., & Myasoedov, N. F. (2006). Neuroprotective and antiamnesic effects of Semax during experimental ischemic infarction of the cerebral cortex. Bulletin of experimental biology and medicine, 142(6), 663-666. https://doi.org/10.1007/s10517-006-0445-0 https://pubmed.ncbi.nlm.nih.gov/17603664/ 

1. 1. Iasnetsov, V. V., & Voronina, T. A. (2009). Eksperimental'naia i klinicheskaia farmakologiia, 72(1), 68-70. https://pubmed.ncbi.nlm.nih.gov/19334516/ 

1. 1. Iasnetsov, V. V., & Ivanov, I.uV. (2004). Farmacologicheskaia korrektsiia mnesticheskikh rasstroĭstv, vyzvannykh kompleksnym ékstremal'nym vozdeĭstiem u mysheĭ s pereviazannymi oshchimi sonnymi arteriiami [Pharmacological correction of memory impairment caused by a complex extremal action in mice with bilateral ligation of common carotid arteries]. Eksperimental'naia i klinicheskaia farmakologiia, 67(5), 3-4. https://pubmed.ncbi.nlm.nih.gov/15559625/ 

1. 1. Silachev, D. N., Shram, S. I., Shakova, F. M., Romanova, G. A., & Myasoedov, N. F. (2009). Formation of spatial memory in rats with ischemic lesions to the prefrontal cortex; effects of a synthetic analog of ACTH(4-7). Neuroscience and behavioral physiology, 39(8), 749-756. https://doi.org/10.1007/s11055-009-9197-4 https://pubmed.ncbi.nlm.nih.gov/19779827/ 

1. 1. Tsai S. J. (2007). Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. Medical hypotheses, 68(5), 1144-1146. https://doi.org/10.1016/j.mehy.2006.07.017 https://pubmed.ncbi.nlm.nih.gov/16996699/

1. 1. Svishcheva, M. V., Mukhina, A. Y., Medvedeva, O. A., Shevchenko, A. V., Bobyntsev, I. I., Kalutskii, P. V., Andreeva, L. A., & Myasoedov, N. F. (2020). Composition of Colon Microbiota in Rats Treated with ACTH(4-7)-PGP Peptide (Semax) under Conditions of Restraint Stress. Bulletin of experimental biology and medicine, 169(3), 357-360. https://doi.org/10.1007/s10517-020-04886-7  https://pubmed.ncbi.nlm.nih.gov/32737723/  

1. 1. Svishcheva, M. V., Mishina, Y. S., Medvedeva, O. A., Bobyntsev, I. I., Mukhina, A. Y., Kalutskii, P. V., Andreeva, L. A., & Myasoedov, N. F. (2021). Morphofunctional State of the Large Intestine in Rats under Conditions of Restraint Stress and Administration of Peptide ACTH(4-7)-PGP (Semax). Bulletin of experimental biology and medicine, 170(3), 384-388. https://doi.org/10.1007/s10517-021-05072-z  https://pubmed.ncbi.nlm.nih.gov/33459919/  

1. 1. Ivanikov, I. O., Brekhova, M. E., Samonina, G. E., Myasoedov, N. F., & Ashmarin, I. P. (2002). Therapy of peptic ulcer with semax peptide. Bulletin of experimental biology and medicine, 134(1), 73-74. https://doi.org/10.1023/a:1020621124776  https://pubmed.ncbi.nlm.nih.gov/12459874/  

1. 1. Zhuikova, S. E., Sergeev, V. I., Samonina, G. E., & Myasoedov, N. F. (2002). Possible mechanism underlying the effect of Semax on the formation of indomethacin-induced ulcers in rats. Bulletin of experimental biology and medicine, 133(6), 577-579. https://doi.org/10.1023/a:1020285909696 https://pubmed.ncbi.nlm.nih.gov/12447470/  

1. 1. Zhuĭkova, S. E., Badmaeva, K. E., Samonina, G. E., & Plesskaia, L. G. (2003). Semaks i nekotorye gliprolinovye peptidy uskoriaiut zazhivlenie atsetatnykh iazv u krys [Semax and some glyproline peptides accelerate the healing of acetic ulcers in rats]. Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology, (4), 88-117. https://pubmed.ncbi.nlm.nih.gov/14653248/   

1. 1. Zhuikova, S. E., Smirnova, E. A., Bakaeva, Z. V., Samonina, G. E., & Ashmarin, I. P. (2000). Effect of Semax on homeostasis of gastric mucosa in albino rats. Bulletin of experimental biology and medicine, 130(9), 871-873. https://pubmed.ncbi.nlm.nih.gov/11177268/

1. 1. Gusev, E. I., Skvortsova, V. I., & Chukanova, E. I. (2005). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 105(2), 35-40. https://pubmed.ncbi.nlm.nih.gov/15792140/   

1. 1. Golubeva, A. V., Gavrilova, S. A., Lipina, T. V., Shornikova, M. V., Postnikov, A. B., Andreeva, L. A., Chentsov, I.uS., & Koshelev, V. B. (2006). Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova, 92(6), 732-745. https://pubmed.ncbi.nlm.nih.gov/16967870/  

1. 1. Gavrilova, S. A., Golubeva, A. V., Lipina, T. V., Fominykh, E. S., Shornikova, M. V., Postnikov, A. B., Andrejeva, L. A., Chentsov, I.uS., & Koshelev, V. B. (2006). Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova, 92(11), 1305-1321. https://pubmed.ncbi.nlm.nih.gov/17385423/  

1. 1. Gorbacheva, A. M., Berdalin, A. B., Stulova, A. N., Nikogosova, A. D., Lin, M. D., Buravkov, S. V., Gavrilova, S. A., & Koshelev, V. B. (2016). Changes in Sympathetic Innervation of Rat Caudal Artery in Experimental Myocardial Infarction. Effect of Semax Peptide. Bulletin of experimental biology and medicine, 161(4), 476-480. https://doi.org/10.1007/s10517-016-3442-y  https://pubmed.ncbi.nlm.nih.gov/27591879/

1. 1. Polunin, G. S., Nurieva, S. M., Baiandin, D. L., Sheremet, N. L., & Andreeva, L. A. (2000). Opredelenie terapevticheskoĭ éffektivnosti novogo otechestvennogo preparata "Semaks" pri zabolevaniiakh zritel'nogo nerva [Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease]. Vestnik oftalmologii, 116(1), 15-18. https://pubmed.ncbi.nlm.nih.gov/10741256/  

1. 1. Kurysheva, N. I., Shpak, A. A., Ioĭleva, E. E., Galanter, L. I., Nagornova, N. D., Shubina, N. I.u, & Shlyshalova, N. N. (2001). "Semaks" v lechenii glaukomatoznoĭ opticheskoĭ neĭropatii u bol'nykh s normalizovannym oftal'motonusom [Semax in the treatment of glaucomatous optic neuropathy in patients with normalized ophthalmic tone]. Vestnik oftalmologii, 117(4), 5-8. https://pubmed.ncbi.nlm.nih.gov/11569188/  

1. 1. Manchenko, D. M., Glazova, N. I.u, Levitskaia, N. G., Andreeva, L. A., Kamenskiĭ, A. A., & Miasoedov, N. F. (2010). Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova, 96(10), 1014-1023.  https://pubmed.ncbi.nlm.nih.gov/21268834/   

1. 1. Ivanova, D. M., Levitskaya, N. G., Andreeva, L. A., Kamenskii, A. A., & Myasoedov, N. F. (2007). Comparative study of analgesic potency of ACTH4-10 fragment and its analog semax. Bulletin of experimental biology and medicine, 143(1), 5-8. https://doi.org/10.1007/s10517-007-0002-5 https://pubmed.ncbi.nlm.nih.gov/18018999/

1. 1. Arushanian, E. B., & Popov, A. V. (2008). Eksperimental'naia i klinicheskaia farmakologiia, 71(2), 14-16. https://pubmed.ncbi.nlm.nih.gov/18488900/   

1. 1. Samotrueva, M. A., Yasenyavskaya, A. L., Murtalieva, V. K., Bashkina, O. A., Myasoedov, N. F., Andreeva, L. A., & Karaulov, A. V. (2019). Experimental Substantiation of Application of Semax as a Modulator of Immune Reaction on the Model of "Social" Stress. Bulletin of experimental biology and medicine, 166(6), 754-758. https://doi.org/10.1007/s10517-019-04434-y  https://pubmed.ncbi.nlm.nih.gov/31028579/  

1. 1. Bakhmet, A. A., & Koplik, E. V. (2012). Antistress effect of Semax in the course of recovery of spleen lymphoid structures after the stress in rats with different behavioral activity. Bulletin of experimental biology and medicine, 153(5), 661-663. https://doi.org/10.1007/s10517-012-1792-7 https://pubmed.ncbi.nlm.nih.gov/23113251/  

1. 1. Ivanov, I.uV., & Iasnetsov, V. V. (2000). Vliianie semaksa i meksidola na techenie ostrogo pankreatita u krys [The effect of semax and mexidol on the course of acute pancreatitis in rats]. Eksperimental'naia i klinicheskaia farmakologiia, 63(1), 41-44. https://pubmed.ncbi.nlm.nih.gov/10763109/  

1. 1. Ivanov I.uV. (2000). Ul'trastrukturnye izmeneniia v podzheludochnoĭ zheleze krys s ostrym pankreatitom posle vvedeniia semaksa [Ultrastructural changes in the pancreas of rats with acute pancreatitis after semax administration]. Eksperimental'naia i klinicheskaia farmakologiia, 63(6), 37-38. https://pubmed.ncbi.nlm.nih.gov/11202510/