Semax

Potential Benefits of Semax

• Lowers the risk of heart disease [1-5]
• Boosts immunity [6-7]
• Accelerates wound healing [8-9]
• Improves brain health and performance [10-19]
• Lowers the risk of stroke [20-25]
• Improves mood [26-30]

What is Semax?

Semax is a synthetic peptide drug. It was developed based on the molecular structure of the adrenocorticotropic hormone, which is produced by the pituitary gland. It was originally used in Russia for the prevention and treatment of circulatory disorders such as stroke. It has the ability to enhance cognition, protect brain cells, and ward off depression.

How Semax Works?

Semax works by stimulating certain parts of the brain involved in the release of brain-derived neurotrophic factor (BDNF). BDNF are chemicals involved in neurogenesis (formation of new neurons in the brain) and survival of existing neurons.

Chemical Structure of Semax

Research on Semax

Lowers the Risk of Heart Disease

A number of convincing studies show that Semax can help protect against heart disease:

1. In mice, Semax produced beneficial effects on cardiac remodeling and decreased the risk of heart failure after a heart attack. [1]
2. In mice, administration of Semax prevented the alteration of the heart’s function caused by the restriction of blood supply. [2]
3. A study showed that Semax improved the functions of the cardiovascular system. [3]
4. In rats with experimental myocardial infarction, Semax increased heart rate and reduced stress on the different heart structures. [4]
5. A rat study reported that Semax can help increase heart rate by affecting the electrical conduction system of the heart. [5]

Boosts Immunity

Evidence suggests that Semaxcan help strengthen the immune system:

1. A study reported that Semax’s immune-modulating properties were effective in treating stress-induced immune imbalance. [6]
2. A study also found that Semax can help boost immunity by regulating the activities of immune system cells. [7]

Accelerates Wound Healing

Semax has also been found to possess regenerative properties:

1. A study reported that Semax shortened the healing time of acetic ulcers by reducing inflammation in the ulcer zone. [8]
2. In rats, Semaxinjections inhibited the formation of acetic acid ulcers. [9]

Improves Brain Health and Performance

An overwhelming body of evidence supports the beneficial effects of Semax on brain function:

1. In animal models, intranasal administration of Semaximproved learning and memory. [10]
2. In rats, Semax administration improved cognitive function by stimulating the production of brain-derived neurotrophic factor (BDNF). [11]
3. In mice, Semaxshowed cognitive-enhancing effects with increased BDNF levels. [12]
4. A study suggested that Semax can help treat memory disorders associated with decreased blood supply to the brain. [13]
5. A study showed that Semax can help protect against metal-induced brain toxicity. [14]
6. In rats, intranasal administration of Semax was effective in rapid and specific activation of BDNF and growth factor gene (NGF) in different brain regions. [15]
7. In rats with Parkinson’s disease, Semax improved performance in a test assessing memory. [16]
8. A study found that Semax can help improve learning ability by stabilizing the levels of the anti-stress peptides known as enkephalins. [17]
9. In healthy volunteers, Semax increased the function of the default mode network of the brain. [18]
10. In epileptic mice, Semax provided protective effects against learning and memory deficits. [19]

Lowers the Risk of Stroke

Aside from boosting brain function, Semax also has protective effects against stroke:

1. In patients with cerebrovascular insufficiency, a condition characterized by obstruction in the brain arteries resulting in reduced blood supply, Semax treatment inhibited disease progression and reduced the risk of stroke attacks. [20]
2. A study showed that high doses of Semax (100-150 micrograms/kg) prevented acute ischemic stroke. [21]
3. In rats, Semax protected against injury caused by sudden blood flow to the brain. [22]
4. In patients with stroke, Semax treatment had beneficial effects on the rate of restoration of the damaged neurological functions. [23]
5. In patients who were at different stages of stroke, Semax administration accelerated functional recovery and improved motor performance. [24]
6. A rat study found that Semax prevented stroke by reducing the occlusion of brain arteries. [25]

Improves Mood

Studies also show that Semax has antidepressant and anti-anxiety effects:

1. In white rats, Semax significantly diminished neonatal stress. [26]
2. A study reported that Semax can be a therapeutic option for depression. [27]
3. In rats, Semax administration improved performance in a test assessing anxiety. [28]
4. A rat study also found that Semax injections induced antidepressant and anti-anxiety effects after 1-14 days. [29]
5. In rodents, Semax injections improved mood by increasing the levels of the brain chemical known as dopamine. [30]

Associated Side Effects of Semax

Semax side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on Semax. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of Semax. Despite this, it was listed as a side effect associated with Semax even though these associated side effects are very uncommon.
Side effects associated with Semax may include the following:

• Hair loss
• Discoloration of the nasal cavity
• Increase in blood sugar levels of diabetic patients

References

1. Gavrilova SA, Golubeva AV, Lipina TV, Fominykh ES, Shornikova MV, Postnikov AB, Andrejeva LA, ChentsovIuS, Koshelev VB. [Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction]. Ross FiziolZhIm I M Sechenova. 2006 Nov;92(11):1305-21. Russian. PMID: 17385423.
2. Golubeva AV, Gavrilova SA, Lipina TV, Shornikova MV, Postnikov AB, Andreeva LA, ChentsovIuS, Koshelev VB. [Protective effect of peptide semax the rat heart in acute myocardial infarction]. Ross FiziolZhIm I M Sechenova. 2006 Jun;92(6):732-45. Russian. PMID: 16967870.
3. Medvedeva EV, Dmitrieva VG, Povarova OV, Limborska SA, Skvortsova VI, Myasoedov NF, Dergunova LV. 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. 2014 Mar 24;15:228. doi: 10.1186/1471-2164-15-228. PMID: 24661604; PMCID: PMC3987924.
4. Gavrilova SA, Markov MA, Berdalin AB, Kurenkova AD, Koshelev VB. Changes in Sympathetic Innervation of the Heart in Rats with Experimental Myocardial Infarction. Effect of Semax. Bull ExpBiol Med. 2017 Sep;163(5):617-619. doi: 10.1007/s10517-017-3862-3. Epub 2017 Sep 25. PMID: 28948544.
5. Arushanian EB, Popov AV. [Effect of semax on heart rate variability in various daytime periods]. EkspKlinFarmakol. 2009 Mar-Apr;72(2):32-4. Russian. PMID: 19441725.
6. Samotrueva MA, Yasenyavskaya AL, Murtalieva VK, Bashkina OA, Myasoedov NF, Andreeva LA, Karaulov AV. Experimental Substantiation of Application of Semax as a Modulator of Immune Reaction on the Model of “Social” Stress. Bull ExpBiol Med. 2019 Apr;166(6):754-758. doi: 10.1007/s10517-019-04434-y. Epub 2019 Apr 26. PMID: 31028579.
7. Available at https://www.hilarispublisher.com/proceedings/the-action-of-neuroprotective-peptide-semax-on-the-expression-of-genes-affecting-the-activity-of-immune-system-in-rat-brain-focal-ischemia-24589.html.
8. Zhuĭkova SE, Badmaeva KE, Samonina GE, Plesskaia LG. Semaks i nekotoryegliprolinovyepeptidyuskoriaiutzazhivlenieatsetatnykhiazv u krys [Semax and some glyproline peptides accelerate the healing of acetic ulcers in rats]. EkspKlinGastroenterol. 2003;(4):88-92, 117. Russian. PMID: 14653248.
9. Zhuikova SE, Smirnova EA, Bakaeva ZV, Samonina GE, Ashmarin IP. Effect of Semax on homeostasis of gastric mucosa in albino rats. Bull ExpBiol Med. 2000 Sep;130(9):871-3. PMID: 11177268.
10. Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, Dubynina EV, Novosadova EV, Andreeva LA, Alfeeva LY, Kamensky AA, Grivennikov IA, Myasoedov NF, Engele J. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006 Oct 30;1117(1):54-60. doi: 10.1016/j.brainres.2006.07.108. Epub 2006 Sep 22. PMID: 16996037.
11. Dolotov OV, Karpenko EA, Seredenina TS, Inozemtseva LS, Levitskaya NG, Zolotarev YA, Kamensky AA, Grivennikov IA, Engele J, Myasoedov NF. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem. 2006 Apr;97Suppl 1:82-6. doi: 10.1111/j.1471-4159.2006.03658.x. PMID: 16635254.
12. FirstovaIuIu, Dolotov OV, KondrakhineA, Dubynina EV, Grivennikov IA, Kovalev GI. [Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behavior efficacy]. EkspKlinFarmakol. 2009 Nov-Dec;72(6):3-6. Russian. PMID: 20095391.
13. Iasnetsov VV, Krylova IN, Provornova NA. Farmakologicheskaiakorrektsiianarusheniĭmnesticheskikhfunktsiĭ, vyzvannykhgipoksieĭ i ishemieĭgolovnogomozga u krys [Pharmacological treatment of memory disorders caused by hypoxia and cerebral ischemia in rats]. AviakosmEkolog Med. 1998;32(1):55-60. Russian. PMID: 9606516.
14. Tabbì G, Magrì A, Giuffrida A, Lanza V, Pappalardo G, Naletova I, Nicoletti VG, Attanasio F, Rizzarelli E. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity. J InorgBiochem. 2015 Jan;142:39-46. doi: 10.1016/j.jinorgbio.2014.09.008. Epub 2014 Sep 28. PMID: 25310602.
15. AgapovaTIu, AgniullinIaV, Silachev DN, Shadrina MI, Slominskiĭ PA, Shram SI, Limborskaia SA, Miasoedov NF. [Effect of semax on the temporary dynamics of brain-derived neurotrophic factor and nerve growth factor gene expression in the rat hippocampus and frontal cortex]. Mol Gen MikrobiolVirusol. 2008;(3):28-32. Russian. PMID: 18756821.
16. Slominsky PA, Shadrina MI, Kolomin TA, et al. Peptides semax and selank affect the behavior of rats with 6-OHDA induced PD-like parkinsonism. DoklBiol Sci. 2017;474(1):106-109.
17. Kost N. V., Sokolov O., Gabaeva M. V., Grivennikov I. A., Andreeva L. A., Miasoedov N. F., et al. . (2001). Semax and selank inhibit the enkephalin-degrading enzymes from human serum. Bioorg. Khim. 27, 180–183.
18. Lebedeva IS, Panikratova YR, Sokolov OY, Kupriyanov DA, Rumshiskaya AD, Kost NV, Myasoedov NF. Effects of Semax on the Default Mode Network of the Brain. Bull Exp Biol Med. 2018 Sep;165(5):653-656. doi: 10.1007/s10517-018-4234-3. Epub 2018 Sep 17. PMID: 30225715.
19. Scantlebury MH, Chun KC, Ma SC, Rho JM, Kim DY. Adrenocorticotropic hormone protects learning and memory function in epileptic Kcna1-null mice. Neurosci Lett. 2017 Apr 3;645:14-18. doi: 10.1016/j.neulet.2017.02.069. Epub 2017 Feb 27. PMID: 28249786; PMCID: PMC5774237.
20. Gusev EI, Skvortsova VI, Chukanova EI. [Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency].ZhNevrolPsikhiatrIm S SKorsakova. 2005;105(2):35-40. Russian. PMID: 15792140.
21. Miasoedova NF, Skvortsova VI, Nasonov EL, ZhuravlevaEIu, Grivennikov IA, Arsen’eva EL, Sukhanov II. Izucheniemekhanizmovneĭroprotektivnogodeĭstviiasemaksa v ostromperiodeishemicheskogoinsul’ta [Investigation of mechanisms of neuro-protective effect of semax in acute period of ischemic stroke].ZhNevrolPsikhiatrIm S SKorsakova. 1999;99(5):15-9. Russian. PMID: 10358912.
22. Filippenkov IB, Stavchansky VV, Denisova AE, et al. Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats. Genes (Basel). 2020;11(6):681. Published 2020 Jun 22. doi:10.3390/genes11060681.
23. Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat’ko VN, ZhuravlevaEIu, Vanichkin AV. Effektivnost’ semaksa v ostromperiodepolusharnogoishemicheskogoinsul’ta (klinicheskoe i élektrofiziologicheskoeissledovanie) [Effectiveness of semax in acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)]. ZhNevrolPsikhiatrIm S SKorsakova. 1997;97(6):26-34. Russian. PMID: 11517472.
24. Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN. Éffektivnost’ semaksaprilecheniibol’nykhnaraznykhstadiiakhishemicheskogoinsul’ta [The efficacy of semax in the tretament of patients at different stages of ischemic stroke]. ZhNevrolPsikhiatrIm S SKorsakova. 2018;118(3. Vyp. 2):61-68. Russian. doi: 10.17116/jnevro20181183261-68. PMID: 29798983.
25. Stavchanskiĭ VV, Tvorogova TV, BotsinaAIu, Skvortsova VI, Limborskaia SA, Miasoedov NF, Dergunova LV. [The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia]. MolBiol (Mosk). 2011 Nov-Dec;45(6):1026-35. Russian. PMID: 22295573.
26. Volodina MA, Sebentsova EA, Glazova NY, et al. Correction of long-lasting negative effects of neonatal isolation in white rats using semax. ActaNaturae. 2012;4(1):86-92.
27. Pae CU. Therapeutic possibility of “Semax” for depression. CNS Spectr. 2008 Jan;13(1):20-1. doi: 10.1017/s1092852900016102. PMID: 18204410.
28. Levitskaia NG, Vilenskiĭ DA, Sebentsova EA, Anreeva LA, Kamenskiĭ AA, Miasoedov NF. [Influence of Semax on the emotional state of white rats in the norm and against the background of cholecystokinin-tetrapeptide action]. IzvAkadNaukSer Biol. 2010 Mar-Apr;(2):231-7. Russian. PMID: 20387390.
29. Vilenskiĭ DA, Levitskaia NG, Andreeva LA, AlfeevaLIu, Kamenskiĭ AA, Miasoedov NF. [Effects of chronic Semax administration on exploratory activity and emotional reaction in white rats]. Ross FiziolZhIm I M Sechenova. 2007 Jun;93(6):661-9. Russian. PMID: 17850024.
30. Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents. Neurochem Res. 2005 Dec;30(12):1493-500. doi: 10.1007/s11064-005-8826-8. PMID: 16362768.