N-Acetyl Semax Amidate | Reviews, Clinical Studies, and Safety

N-Acetyl Semax Amidate is a modified version of Semax peptide, but with improved stability and enhanced potency. It is currently studied for a range of nootropic and neuroprotective effects, including information retention and mood regulation. Inside, scientists will find what they MUST know about N-Acetyl Semax Amidate.

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    Compound Overview

    Class of Compound:

    Peptide

    Mechanism of Action:

    N-Acetyl Semax Amidate is thought to have similar mechanisms of action to Semax with improved pharmacokinetics. Its believed mechanisms include stimulating neurotrophic factors in the central nervous system and interacting with enkephalin, serotonin, and dopamine signaling.

    Notable Studies:

    Also Known As:

    Ac-Met-Glu-His-Phe-Pro-Gly-Pro-NH2

    Research Applications:

    • Cognitive enhancement
    • Neuroprotection
    • Gastroprotection
    • Mood regulation

    Risks:

    • Research limited to Russian studies
    • Lack of regulatory approval outside of Russian and CIS
    • Limited safety data

    Chemical Structure

    N-acetyl semax chemical structure

    What is N-Acetyl Semax Amidate?

    N-Acetyl Semax Amidate is a modified version of the nootropic peptide Semax, the latter of which was originally developed by Russian researchers in the 1980s [1].

    Structurally, both N-Acetyl Semax Amidate and Semax comprise a seven-amino-acid sequence that includes a fragment from adrenocorticotropic hormone, ACTH (4-7), combined with a Pro-Gly-Pro extension at the C-terminus. This allows both peptides to effectively cross the blood-brain barrier (BBB) [2, 3].

    The N-terminal acetylation of Semax has been suggested to result in enhanced resistance to hydrolysis and may also increase the peptide’s ability to reach the binding sites where the molecule exerts its effects [4].

    Therefore, the addition of acetic acid at the N-terminus and amidation at the C-terminus, which results in N-Acetyl Semax Amidate, has been suggested to offer the following advantages:

    • The process of N-terminal acetylation in Semax delivers enhanced stability, making the N-terminus of the peptide resistant to degradation by leucine aminopeptidase [5].
    • The peptide is more resistant to proteolysis in blood plasma enzymes following N-terminal acetylation, and the peptide withstands degradation 30 minutes longer than unmodified Semax [5].
    • Researchers report increased stability in brain tissue following N-terminal acetylation, potentially indicating prolonged effects compared to Semax [6].
    • Amidation at the C-terminus protects the peptide from hydrolysis, further enhancing its stability [7].

    Although research detailing the exact benefits of N-Acetyl Semax Amidate remains limited, the extensive data on Semax can be employed as a reference.

    In clinical research, Semax has been linked to [8, 9, 10, 11, 12]:

    • cognitive enhancement and nootropic effects
    • neuroprotective attributes
    • therapeutic effects in Alzheimer's, traumatic brain injury, and ischemic stroke
    • gastroprotective effects

    N-Acetyl Semax Amidate is available strictly for research purposes, and qualified researchers can legally purchase it online as a nasal spray or as lyophilized powder for injection.

    NA Semax

    How Does N-Acetyl Semax Amidate Work?

    The available literature on N-Acetyl Semax Amidate focuses on its improved pharmacokinetics over regular Semax, while research into its mechanisms and effects is lacking. Nevertheless, N-Acetyl Semax Amidate is expected to work similarly to Semax.

    Below, we outline the mechanisms of Semax, which may be useful for understanding how N-Acetyl Semax Amidate works when administered:

    • Semax has been found to cross the BBB when administered intranasally or via injection to exert its action directly on the brain without ACTH-like effects [13, 14].
    • Upon reaching the brain, the peptide is believed to interact with serotonin, dopamine, and enkephalin (opioid) signaling, which regulate mood, stress, cognition, and reward-related behavior [15, 16, 17].
    • Semax potentially boosts neurogenesis and neuroregeneration by raising brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the brain, which are neurotrophic factors that enhance neurogenesis and neuroregeneration [18]. Studies suggest that Semax enhances BDNF levels by 1.4 times and doubles the expression of related trkB receptors, which are vital for brain cell survival and neuroplasticity [19].

    In addition, Semax may also provide benefits outside the nervous system, such as regulating blood flow, microcirculation, and vascular permeability in the gastrointestinal system.

    By consequence, the peptide may have anti-ulcer effects, but more research is required to confirm its potential in this regard [20].

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    Research Applications and Benefits of N-Acetyl Semax Amidate

    N-Acetyl Semax Amidate, a modified version of the synthetic peptide Semax, is still in preliminary stages of research.

    While direct data on the specific effects of N-Acetyl Semax Amidate remain limited, researchers may refer to studies on Semax to understand the potential implications of the modified version.

    In this section, we cover four key areas in which research into N-Acetyl Semax Amidate may prove fruitful.

    N-Acetyl Semax Amidate and Cognitive Enhancement

    While there is limited direct research on the nootropic effects of N-Acetyl Semax Amidate, insights can be gleaned from studies on Semax, which is officially approved in Russia for therapy in cognitive and neurodegenerative disorders [1].

    Here are some of the most notable findings to date:

    • Nootropic effects in fatigued subjects: Researchers examined the cognitive effects of intranasal Semax on healthy individuals following an 8-hour work shift. Participants were given a single intranasal administration of 16mcg/kg of Semax, with the effects observed for 24 hours. Results indicated that the Semax-treated group achieved 71% accuracy on a memory test, compared to 41% accuracy for the control group participants [21].
    • Increased activity in certain brain areas: One study investigated the impact of Semax on the default mode network (DMN) in the brains of 24 middle-aged study participants. The participants received either a 1% Semax solution or placebo intranasally, with functional magnetic resonance imaging (fMRI) scans conducted before and at 5 and 20 minutes post-administration. Semax increased the volume of the rostral subcomponent of the DMN, especially within the medial frontal cortex, potentially optimizing episodic memory and information processing [22].

    This robust data on Semax provide a useful reference for understanding the potential nootropic effects and benefits of its derivative N-Acetyl Semax Amidate.

    N-Acetyl Semax Amidate and Neuroprotection

    Researchers interested in the neuroprotective potential of N-Acetyl Semax Amidate may consider the available data on Semax, including the fact that it is officially approved in Russia for therapy in stroke. Here are some of the most notable findings in this regard:

    • Recovery of function in stroke: In a trial in 110 stroke patients, intranasal Semax (6000mcg/day over two 10-day courses) led to elevated plasma BDNF levels, resulting in improved motor skills and functional independence [23].
    • Reducing inflammation after stroke: When administered to acute stroke patients, Semax increased anti-inflammatory mediators like interleukin-10 and tumor necrosis factor-alpha while decreasing proinflammatory factors and indicators such as interleukin-8 and C-reactive protein [24].
    • Recovery in chronic brain ischemia: In a study in 30 chronic brain ischemia patients, a combination of Semax, ADP, and collagen yielded better recovery outcomes, emphasizing Semax's neurotrophic and anti-platelet effects [25].
    • Reducing optic nerve damage: Clinical research has indicated that intranasal Semax can mitigate pressure-induced nerve damage in glaucoma patients [26].
    • Reducing alcohol neurotoxicity: A study in 30 alcohol delirium patients, half of whom received Semax, suggested that the peptide can counteract the neurotoxic effects of alcohol intoxication [27].

    N-Acetyl Semax Amidate and Mood Regulation

    Laboratory animal studies on the apparent mood-enhancing effects of Semax may be used as a reference for N-Acetyl Semax Amidate's potential.

    For example, one study in rats investigated the impact of intranasal Semax (at doses of 50 and 500mcg/kg) on anxiety and depression levels.

    Semax showed no noticeable changes in rats under normal conditions, but it effectively countered the behavioral disturbances triggered by cholecystokinin-tetrapeptide (CCK-4)—a substance commonly used to mimic anxiety disorders.

    This hints at the potential of Semax as an anxiety and depression alleviator during heightened states of distress [28].

    N-Acetyl Semax Amidate and Anti-Ulcer Potential

    Based on the clinical effectiveness of Semax in promoting the healing of peptic ulcers, N-Acetyl Semax Amidate may have similar potential. One trial found that using a 1% Semax solution intranasally led to a peptic ulcer healing rate of 90%, which was almost three times higher than the healing rate observed with the placebo group.

    In the study, participants in the treatment group were administered 2-4 drops (500mcg per drop) of Semax in each nostril thrice daily for 10 days.

    The study authors hypothesized that Semax might exert its anti-ulcer effects by regulating blood flow, microcirculation, and vascular permeability, though further investigations are needed to validate these potential mechanisms [20].

    NA Semax

    N-Acetyl Semax Amidate Dosing | Research Only

    There is no official or safe N-Acetyl Semax Amidate dosage for either nasal spray or injectable formulations.

    Therefore, researchers may consider referring to prevalent Semax dosing guidelines as a guide.

    Nasal Spray Dosing and Administration

    In designing a N-Acetyl Semax Amidate nasal spray dosing protocol, scientists may refer to guidelines for intranasal Semax, which is officially approved in Russia as 0.1% nasal drops and 1% nasal drops [1].

    Based on the corresponding package inserts, Semax is administered as follows [29, 30]:

    • 0.1% Semax nasal drops deliver 50mcg of the peptide per drop. They can be administered for mental fatigue in doses of 400–900mcg/daily, divided into two to three daily doses for 3-5 days.
    • Severe cases of cognitive impairment, such as those involving cerebrovascular lesions or dyscirculatory encephalopathy, can be managed with 0.1% Semax in doses of 800–8000mcg (equivalent to 7–70mcg/kg), divided into four daily doses for 10-14 days.
    • Semax 1% delivers 500mcg per drop and can be applied in stroke patients. Moderate cases are given 2000mcg-3000mcg per application, three to four times daily. Severe cases are treated with 3000mcg-4000mcg per application, given four to six times daily. The peptide can be administered at 3+ hour intervals for up to 10 days.

    When administered to stroke patients, 1% Semax can be cycled at doses of 6000mcg/daily, with 10 days on and 20 days off, followed by another 10 days of administration [31].

    By contrast, intranasal N-Acetyl Semax Amidate is generally available for research as either a 0.3% or a 0.1% nasal spray, both of which deliver 300mcg of the peptide per pump.

    Based on the aforementioned Semax recommendations, experts suggest the following dosing protocol for nootropic research with N-Acetyl Semax Amidate:

    • Recommended Dosage: Begin with a daily dose of 600mcg, and adjust based on the subject's response.
    • Study Duration: Do not exceed 30 days at 900mcg/daily or higher, or up to 60 days at 600mcg/daily.
    • N-Acetyl Semax Amidate Cycle: Provide a washout period equal to the length of the study.
    • Notes: Continuously monitor the subjects’ EEG indicators and for neurological, psychological, and physical responses to the peptide.

    Researchers may refer to the following steps for safely administering N-Acetyl Semax Amidate nasal spray:

    • Clear the subject’s nostrils.
    • Remove the spray bottle cap and disinfect the nozzle.
    • Slightly tilt back the subject's head.
    • Insert the nozzle into the nostril and depress the sprayer as the subject inhales gently.
    • Rotate to the other nostril and repeat. Wait 60 seconds between sprays to the same nostril.
    • Instruct the subject to refrain from sneezing or blowing their nose for a few minutes.
    • Disinfect the nozzle and place the cap back on.
    • Refrigerate the nasal spray bottle at 36-46 degrees F.

    Dosing and Administration of Injectable Formulations

    There are no official or safe dosage guidelines for N-Acetyl Semax Amidate injections. Reliable data on Semax injections are also scarce, as studies have been conducted primarily in laboratory animals.

    Based on anecdotal information, N-Acetyl Semax Amidate injections are applied in doses of 500mcg-1000mcg/daily for 1-2 months. Here is a reference dosing protocol for this type of formulation:

    • Daily Dosage: Administer 500mcg-1000mcg of N-Acetyl Semax Amidate subcutaneously, adjusting based on the subject’s response.
    • Study Duration: Maximum 30 days at 1000mcg/daily, or up to 60 days at 500mcg/daily.
    • N-Acetyl Semax Amidate Cycle: Implement a rest period matching the study length.
    • Notes: One 30mg N-Acetyl Semax Amidate vial yields 30 doses at 1000mcg/daily, or 60 doses at the 500mcg dose. Continuously track the subjects' neurological, psychological, and physical health and any EEG changes.

    Injectable N-Acetyl Semax Amidate must be reconstituted with bacteriostatic water and then administered to test subjects via subcutaneous injection, following these safety tips:

    • Wash hands thoroughly.
    • Choose the site of injection. Common areas include the abdomen (2 inches from the navel), thighs, and upper arm.
    • Clean the site with an alcohol swab.
    • Pinch a skin fold at the site of injection and insert the needle at a 45° angle.
    • Release the skin and slowly inject the peptide.
    • Swiftly withdraw the needle and safely dispose of it.
    • Refrigerate the peptide at 36-46 degrees F.

    N-Acetyl Semax Amidate Side Effects and Safety

    Unfortunately, there is a paucity of clinical research into the safety and side effects of N-Acetyl Semax Amidate. Therefore, researchers may reference the available safety data on intranasal Semax.

    Semax has been used safely in intranasal doses ranging from 600mcg/daily to 12mg/daily, with trials of up to 30 days reporting no major side effects [25, 32, 33].

    Nevertheless, some researchers suggest that Semax may have stimulant-like effects that can lead to increased anxiety levels in some subjects [21].

    Out of an abundance of caution, researchers should accordingly avoid co-administering other nootropics with N-Acetyl Semax Amidate. Intranasal delivery may also lead to nose and throat irritation and discomfort.

    There is likewise a lack of clinical data on the safety of injectable N-Acetyl Semax Amidate or its unmodified counterpart. As of writing, available laboratory animal studies on Semax do not report any side effects [12, 13, 34, 35].

    Still, researchers should remember that peptide injections can lead to local reactions at the injection site, such as pain, swelling, redness, and induration.

    Where to Buy N-Acetyl Semax Amidate Online? | 2024 Edition

    Researchers looking to explore the vast potential of N-Acetyl Semax Amidate are well-advised to source the peptide from a reputable vendor that prioritizes product purity and customer satisfaction.

    The team at Peptides.org has tested a variety of peptide sources, and the following vendor stands out as our favorite choice for superior N-Acetyl Semax Amidate nasal sprays and related products.

    Limitless Life

    Limitless Life provides research-grade N-Acetyl Semax Amidate nasal spray along with stellar customer service.

    Here's why they stand out as our go-to vendor:

    • Made in the United States: Limitless Life’s research-grade compounds are synthesized in registered US facilities. Comprehensive third-party laboratory reports provide assurance of this vendor’s commitment to product purity and consistency.
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    • Quick Shipping: The vendor charges a low flat shipping fee on all orders, and waives the fee on domestic order of $350+. Orders are dispatched quickly and typically arrive to U.S.-based researchers in 2-3 days.

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    N-Acetyl Semax Amidate vs. Semax

    Researchers looking to uncover the potential of N-Acetyl Semax Amidate may wonder how this peptide compares to its unmodified counterpart regarding pharmacokinetics, regulatory status, and potential benefits.

    Stability and Pharmacokinetics

    Semax has been shown to penetrate the BBB when delivered intranasally or via subcutaneous injection [2, 3].

    N-Acetyl Semax Amidate is likewise expected to penetrate the BBB and exert even greater bioavailability, given its superior stability in both blood plasma and brain tissue.

    This increased stability stems from the acetylation and amidation processes, which shield the peptide's N- and C-terminal groups from enzymatic breakdown [5, 6].

    Research and Approval

    Semax was initially developed in Russia and has undergone thorough scrutiny by that country’s regulators. The peptide is authorized for use in Russia in the management of various neurological conditions such as mental fatigue, cognitive impairment, and stroke [1]. In the United States, Semax is available as a research peptide.

    N-Acetyl Semax Amidate has not undergone any extensive clinical study in any country, and is likewise generally available as a research chemical.

    Effects and Benefits

    Semax has been linked to cognitive enhancement and potential neuroprotective qualities. N-Acetyl Semax Amidate is believed to offer similar benefits—possibly even more pronounced due to its enhanced pharmacokinetics. Yet, current research is insufficient to firmly support this assertion.

    Nevertheless, preliminary research suggests increased stability of N-Acetyl Semax Amidate in brain tissue compared to its unmodified version, which may indicate prolonged nootropic and neuroprotective effects [6].

    N-Acetyl Semax Amidate Review

    N-Acetyl Semax Amidate is believed to offer a spectrum of cognitive and neurological advantages akin to those attributed to Semax, such as neuroregeneration, enhanced neuroplasticity, and amplified memory and attention span.

    Like unmodified Semax, N-Acetyl Semax Amidate is generally classified as a research peptide. Comprehensive clinical research is warranted to develop a clearer picture of its potential benefits and side effects.

    Therefore, researchers are advised to exercise caution when administering N-Acetyl Semax Amidate in an investigative setting.

    Qualified professionals may buy research-grade N-Acetyl Semax Amidate nasal spray from our top recommended vendor.

    References

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    3. Khavinson V, Diomede F, Mironova E, Linkova N, Trofimova S, Trubiani O, Caputi S, Sinjari B. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism. Molecules. 2020 Jan 30;25(3):609. doi: 10.3390/molecules25030609. PMID: 32019204; PMCID: PMC7037223
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    6. Anisimov VN, Khavinson VK, Provinciali M, Alimova IN, Baturin DA, Popovich IG, Zabezhinski MA, Imyanitov EN, Mancini R, Franceschi C. Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2002 Sep 1;101(1):7-10. doi: 10.1002/ijc.10570. PMID: 12209581.
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    12. Korkushko OV, Khavinson VKh, Shatilo VB, Magdich LV. Effect of peptide preparation epithalamin on circadian rhythm of epiphyseal melatonin-producing function in elderly people. Bull Exp Biol Med. 2004 Apr;137(4):389-91. doi: 10.1023/b:bebm.0000035139.31138.bf. PMID: 15452611.
    13. Korenevsky AV, Milyutina YP, Bukalyov AV, Baranova YP, Vinogradova IA, Arutjunyan AV. [Protective effect of melatonin and epithalon on hypothalamic regulation of reproduction in female rats in its premature aging model and on estrous cycles in senescent animals in various lighting regimes]. Adv Gerontol. 2013;26(2):263-274. Russian. PMID: 28976150.
    14. Chitimus DM, Popescu MR, Voiculescu SE, Panaitescu AM, Pavel B, Zagrean L, Zagrean AM. Melatonin's Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease. Biomolecules. 2020 Aug 20;10(9):1211. doi: 10.3390/biom10091211. PMID: 32825327; PMCID: PMC7563541.
    15. Rosenfeld SV, Togo EF, Mikheev VS, Popovich IG, Khavinson VKh, Anisimov VN. Effect of epithalon on the incidence of chromosome aberrations in senescence-accelerated mice. Bull Exp Biol Med. 2002 Mar;133(3):274-6. doi: 10.1023/a:1015899003974. PMID: 12360351.
    16. Sibarov DA, Vol'nova AB, Frolov DS, Nozdrachev AD. Effects of intranasal administration of epitalon on neuron activity in the rat neocortex. Neurosci Behav Physiol. 2007 Nov;37(9):889-93. doi: 10.1007/s11055-007-0095-3. PMID: 17955380.
    17. Khavinson VKh, Linkova NS, Kvetnoy IM, Kvetnaia TV, Polyakova VO, Korf HW. Molecular cellular mechanisms of peptide regulation of melatonin synthesis in pinealocyte culture. Bull Exp Biol Med. 2012 Jun;153(2):255-8. English, Russian. doi: 10.1007/s10517-012-1689-5. PMID: 22816096.
    18. Anisimov VN, Mylnikov SV, Oparina TI, Khavinson VK. Effect of melatonin and pineal peptide preparation epithalamin on life span and free radical oxidation in Drosophila melanogaster. Mech Ageing Dev. 1997 Aug;97(2):81-91. doi: 10.1016/s0047-6374(97)01897-6. PMID: 9226628.
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    20. Kozina LS, Arutjunyan AV, Khavinson VKh. Antioxidant properties of geroprotective peptides of the pineal gland. Arch Gerontol Geriatr. 2007;44 Suppl 1:213-6. doi: 10.1016/j.archger.2007.01.029. PMID: 17317455.
    21. Anisimov VN, Khavinsov VKh, Alimova IN, Provintsiali M, Manchini R, Francheski K. Epithalon inhibits tumor growth and expression of HER-2/neu oncogene in breast tumors in transgenic mice characterized by accelerated aging. Bull Exp Biol Med. 2002 Feb;133(2):167-70. doi: 10.1023/a:1015555023692. PMID: 12428286.
    22. Kossoy G, Anisimov VN, Ben-Hur H, Kossoy N, Zusman I. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo. 2006 Mar-Apr;20(2):253-7. PMID: 16634527.
    23. Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VKh, Anisimov VN. Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes. Bull Exp Biol Med. 2007 Dec;144(6):825-30. doi: 10.1007/s10517-007-0441-z. PMID: 18856211.
    24. Vinogradova IA, Bukalev AV, Zabezhinski MA, Semenchenko AV, Khavinson VKh, Anisimov VN. Geroprotective effect of ala-glu-asp-gly peptide in male rats exposed to different illumination regimens. Bull Exp Biol Med. 2008 Apr;145(4):472-7. doi: 10.1007/s10517-008-0121-7. PMID: 19110597.
    25. Korkushko OV, Khavinson VKh, Shatilo VB, Antonyk-Sheglova IA. Peptide geroprotector from the pituitary gland inhibits rapid aging of elderly people: results of 15-year follow-up. Bull Exp Biol Med. 2011 Jul;151(3):366-9. English, Russian. doi: 10.1007/s10517-011-1332-x. PMID: 22451889.
    26. Epithalon monograph final - peptidesociety.org. https://peptidesociety.org/wp-content/uploads/2018/07/Epithalon-Monograph-Final.pdf (Accessed November 9, 2022).