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Semax

Semax Peptide,  Met-Glu-His-Phe-Pro-Gly-Pro

Semax Peptide, Met-Glu-His-Phe-Pro-Gly-Pro

 

Looking To Buy Semax?

usa iconUSA and Worldwide: Ceretropic. who offer 60mg and 120mg vials of lyophilised powder.
eu icon uk flagEuropean Union and United Kingdom: SmartNootropics who offer the Semax nose dropper in 1% and 0.1%.

Important Information

The 1% and 0.1% solutions of Semax available in Russia.

The 1% and 0.1% solutions of Semax available in Russia.

Dosage Guide

For nootropic purposes, a dose 0.25-1mg per day would seem suitable. A single dose is sufficient for the entire day and possibly beyond. Intranasal or Sub-Q administration are the only accepted ways of administering Semax. Do not consume by mouth or sublingually as Semax will be rendered inactive.

Lyophilised Semax will require reconstitution with sterile water before being suitable for injection or intranasal administration.

Making A Semax Nasal Spray

This can be done easily enough with a metered nasal spray. A great guide is found here.

Other Names

Semax Peptide,  Met-Glu-His-Phe-Pro-Gly-Pro

Background Information

Semax is a heptapeptide developed by the Institute of Molecular Genetics, Russian Academy Of Science (IMG RAS)[1]. Semax was likely first developed in the 1980’s to early 1990’s and received authorization for marketing in 1994.[1]. In Russia, Semax is used to treat stroke, brain damage following ischemia, optic nerve disease and as a treatment for various cognitive disorders[2]. Additionally Semax has been shown in one human study to directly enhance cognitive function and favorably alter EEG bands.

Structure

Structurally, Semax is an analog of adrenocorticotropic hormone 4-10 (ACTH 4-10), a fragment of ACTH known for its neurological effects and absence of hormonal effects.  While ACTH 4-10 sequence of amino acids is Met-Glu-His-Phe-Arg-Trp-Gly, Semax is slightly different; Met-Glu-His-Phe-Pro-Gly-Pro.

The addition of the PGP sequence to the C-terminus of ACHT 4-10 is thought to be the reason Semax is so biologically active and possesses a more prolonged effect than ACHT 4-10 [3]. While the natural 4-10 fragment is degreaded into amino acids in the blood, Semax is degraded into a more stable intermediate peptide – Glu-His-Phe-Pro-Gly-Pro.

Benefits of Semax

Cognitive Enhancement

A 2 day study of Russian power plant workers tested the efficacy of Semax with a number memorization task.[4] In total the test lasted around 15 minutes and one was performed at the beginning and end of the workers’ shifts on days 1 and 2 respectively.

A dose of 1mg was given intranasally on day one around 1 hour prior to testing and on day two shortly after the morning’s tests. A placebo group was also requested to perform the same task.

semax2

Semax dramatically decreased the number of incorrect responses on days one and two while the placebo group’s error rate actually increased (see above).  Semax also attenuated a decrease in correct performance scores compared to placebo.

Mood

Animal studies reveal Semax is a potential mood enhancer and anxiety reducing compound. A study of in rats revealed Semax to be capable of attenuating CCK-4 induced stress and depression, while not affecting rats administered placebo.[5]

semax3

CCK-4 is a potent neuropeptide capable of inducing anxiety in humans and animals, so much so, CCK-4 is used to induce panic attacks when researchers are searching for treatment options. Essentially this study demonstrated that rats given nothing or Semax were similar in mood states, while rats given CCK-4 were markedly more depressed and anxious during a forced swim and maze test.

The combination of both CCK-4 and Semax brought rats back to placebo levels in certain parameters of mood, suggesting Semax is capable of treating an anxious and depressed state, while leaving a “normal” state unchanged.

A study abstract featured in the international journal of psychophysiology discussed how both Semax and Selank were capable of producing sedative effects and relieving some effects of mental illness in primates. The full study doesn’t appear to be available online as of July 2014. [6]

Another abstract featured in the Journal for European Neuropsychopharmacology briefly discussed a study with Semax involving delirium following alcohol withdrawal. Semax was found to reduce the time of acute psychotic disturbances (1-5 days) compared to placebo (1-9 days) when administered at a dose of 0.6mg per day intranasally. [7] Following acute symptoms subsiding, Semax at 0.3mg/day was found to improve cognitive function and decrease asthenic disorders relative to placebo. No side effects were noted.

Migraines

A study conducted in 1995 sought to test the analgesic activity of Semax and if it could be suitable for headache and migrane relief. The study featured 3 groups of patients; group 1 was 12 individuals suffering from migraines, group 2 included 16 patients suffering with trigeminal neuralgia while group 3 included 9 patients suffering with dental plexalgia.

semax4

A single dose of 5mcg/KG Semax was found to be helpful for the severity and subjective perception of pain measured by the modified pain sensitivity test (MPST) for both dental plexalgia and migraine. Frequency of pain attacks was not reduced.  Acute effects were noted in as little as 30 minutes with peak effects being found at 60-90 minutes.

Potentiation Of Stimulants

Semax has been found to directly enhance the dopamine release induced by dextroamphetamine in rodents: 20 pmol/ml extracellular DA vs 36-38 pmol/ml with Semax added.

Semax was also found to enhance dextroampethamine increased locomotor activity when compared to dextroampetamine alone (182% vs 261%).

Interestingly Semax alone did not alter locomotor or extracellular DA levels, suggesting a potentiation effect of the dopaminergic system rather than Semax being a direct stimulant.

Semax’s Mechanism Of Action

BDNF and NGF

In glial cell cultures, both BDNF and NGF levels were increased 8 fold and 5 fold following exposure to Semax [8]. In rodents, Semax has been shown to increase BDNF and trkB levels by 1.4 and 1.6 fold respectively [9]. Further research has shown intranasal administration of Semax is able to increase BDNF in the rat brain[10].

Melanocortin Receptor Interactions

The melanocortin system is involved with a diverse number of functions in the body, including energy balance, food intake, immunomodulation and cardiovascular function[11]. Additionally the MC4 receptor is thought to play a role in emotional behavior and the stress response. [12]

ACHT 4-10, the fragment that Semax is based upon, is a melanocortin 4 (mc4) agonist[13] and is considered anxiogenic. Semax has been considered to be an antagonist of the mc4 receptor given its anxiolytic effects[14][15]. These anxiolytic effects may be related to activation of the serotonergic system.

Serotonin

sero

A study involving two groups of animals (mice and rats), measured striatal and hypothalamic levels of dopamine, serotonin and their respective metabolites following Semax injection.

A rise in hypothalamic and striatal 5-HIAA levels were noted both 30 and 120 minutes following Semax injection in the mice group indicating an increase of serotonin turnover.

The second group, involving rats, noted a clear increase of striatum 5-HIAA, with 0.6mg/kg being more pronounced than 0.15mg, but both being statistically significant. Researchers speculated that the effects of Semax on the serotoninergic system may be related to melanocortin receptor antagonism.

A study of rodents being administered CCK-4, a panic inducing; anxiogenic peptide demonstrated Semax was able to attenuate the stressor effects of the compound. Given that this is traditionally done with SSRI drugs and a reduction in serotonin turnover typically gives rise to anxiety and depression the authors speculated that Semax operates to reduce anxiety by enhancing serotonin turnover. [5]

Alpha Brain Waves

Semax has been shown to alter EEG in humans during both a cognitive test and a hyperventilation challenge. During a cognitive test, Semax significantly reduced delta brainwave activity and increased the relative power of alpha and beta brain rhythm (4). Image below.

semax6

During a hyperventilation challenge, Semax prevented negative EEG changes (4). The placebo group experienced an increase in delta and theta brainwaves and a decrease in alpha 1 and 2 brainwaves and the administration of Semax 45 minutes prior nearly totally prevented the negative brainwave changes.

Safety

Semax would appear to be safe and nontoxic.  In Russia, Semax is included in the list of vital and essential drugs (VED) [16], where it Is approved for a number of medical conditions including stroke, cognitive disorders and migraine.

In Russia, Semax has been tested extensively and has featured in a number of human clinical trials and has been reported to be free of side effects and hormonal activity. [1] [4][8].

References

[1] http://old.img.ras.ru/Semax1-e.htm

[2] http://www.ncbi.nlm.nih.gov/pubmed/11569188

[3] http://www.ncbi.nlm.nih.gov/pubmed/16212268

[4] http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1520-6769(199609)19:2%3C115::AID-NRC171%3E3.0.CO;2-B/abstract

[5] http://www.ncbi.nlm.nih.gov/pubmed/20387390

[6] http://www.deepdyve.com/lp/elsevier/the-cerebroprotective-effects-of-Semax-and-selank-in-primates-at-gHqfNvoDEw

[7] http://www.researchgate.net/publication/247138403_P.6.020_
Use_of_the_neurometabolic_drug_Semax_for_complex_treatment_of_alcohol_delirium

[8] http://www.scirp.org/journal/PaperInformation.aspx?PaperID=40560#.U9VYWfldVWg

[9] http://www.sciencedirect.com/science/article/pii/S0006899306022955

[10] http://link.springer.com/article/10.1023%2FA%3A1025177812262

[11] http://ajpendo.physiology.org/content/284/3/E468.long

[12] http://www.ncbi.nlm.nih.gov/pubmed/15740781?dopt=Abstract

[13] http://www.ncbi.nlm.nih.gov/pubmed/21629206

[14] http://link.springer.com/article/10.1023/B%3ADOBS.0000017114.24474.40

[15] http://www.ncbi.nlm.nih.gov/pubmed/7895772

[16] http://mashkovsky.ru/tiki-index.php?page=%D0%A1%D0%B5%D0%BC%D0%B0%D0%BA%D1%81