Semax peptide is a synthetic polypeptide analog of the natural hormone fragment: adrenocorticotropic hormone fragment 4-10 (ACTH 4-10) (2). ACTH fragment 4-10 is a peptide fragment from the adrenocorticotropic hormone secreted by the anterior pituitary gland. This fragment has been reported by researchers not to exhibit any action characteristic of ACTH itself but may have a proposed specific action on the brain (3).
Several naturally occurring peptides perform various biological functions and govern the main regulatory systems in an organism, including the nervous system. However, naturally occurring peptides may exhibit instability and may be easily degradable by the biological enzymes found in gastrointestinal and cerebrospinal fluids, amongst others. Consequently, researchers aim to synthesize analogs of such naturally occurring peptides, aiming to develop synthetics that demonstrate similar biological action and are highly stable in nature.
Synthetically developed Semax has been widely researched for its potential mechanism of action and evaluated for its stability. Researchers suggested it may inhibit selected enzymes which regulate the degradation of enkephalins. Enkephalins are the naturally released neurotransmitters, mainly secreted in the brain, which scientists consider to regulate several biological functions. In addition to enkephalins, Semax may also inhibit other peptide degrading secreted enzymes.
Based on a research study (7), it was suggested that Semax may induce elevated secretion and release of dopamine as well as possibly increasing the levels of brain derived neurotrophic factor (BDNF). Based on another research study (8), Semax may also present the potential to alter the gene expressions which modulate the immune system. In altering gene expression, the levels of immune cells as well as their mobility may be elevated. Semax was reported by researchers to exhibit altering potential in the encoding of chemokines and immunoglobulins, related to the functioning of the vascular system.
Research Studies and Clinical Trials
Semax Peptide and Nootropic Action
This initial study (9) was conducted on ACTH hormone and its analogs, including Semax, to determine its nootropic potential in rodents. After the peptide was given, the levels of 5-hydroxyindoleacetic acid (5-HIAA) were monitored. 5-HIAA levels appeared elevated by 25% after 2 hours of Semax presence. The levels appeared to increase gradually up to a maximum of 180% within 4 hours of peptide presence. It was noted by researchers that the peptide, when given 20 minutes prior to D-amphetamine, appeared to lead to an elevation of 5-HIAA as compared to Semax alone.
Semax Peptide and Neonatal Anxiety
The main aim of this study (10) was to expose neonatal rats to an SSRI and then present Semax to study its potential action. Rats aged between 1 and 14 days received an SSRI, followed by Semax on days 15 to 28. After 28 days, it was noted that upon exposure to the SSRI, the rats exhibited a perceived anxiety-like behavior, where they exhibited an apparently impaired response to stress and new stimuli during the first fourteen days. When Semax was given, these SSRI induced actions appeared altered, with the rats apparently exhibiting improved learning abilities and reduction in anxiety. Researchers posited that Semax might have reestablished normal levels of monoamines in the rodent’s brain, which was initially decreased by the SSRI.
Semax Peptide and the Vascular System
In this study (11), the potential of Semax to protect the rat heart from vascular damage after myocardial infarction (MI) was studied. The rats experienced myocardial infarction, were operated on, and some rats were given Semax for the following 6 days. On the 28th day, after the myocardial infarction, it was reported by the researchers that the rats without Semax appeared to develop cardiac hypertrophy along with decreased arterial blood pressure. Semax rats apparently exhibited signs indicating prevention of the diastolic pressure growth in the left ventricle, with apparent left ventricle remodeling.
Semax Peptide and Neonatal Deprivation
Adolescent rats (12) were separated from their mothers for approximately 5 hours per day during postnatal days 1 to 14. From days 15 to 28, these adolescent rats were then given Semax. After 28 days, it was found that during the time of maternal deprivation, when Semax was not present, there was an apparent increased anxiety and increased physical and emotional reactivity in the rats. Upon Semax presence, researchers reported that reactions and anxiety in the rats appeared restored to control levels.
Semax Peptide and Neuroprotection
This clinical trial (13) was conducted on 100 test subjects with ischemic stroke. 30 subjects were given Semax, whereas the rest were part of the controlled group. Following the study, researchers repoted that when Semax was present, there appeared to be some improvement in the restoration rate of damaged neurological functions. All results were analyzed with the help of EEG mapping.
Semax Peptide and Nootropic Properties
A small-scale clinical trial (14) was conducted where male test subjects were given Semax under high stress conditions, and brain activity monitored. At the end of the study, after about 24 hours, it was reported by the researchers that compared to normal, pre-trial existence, the subjects appeared to exhibit increased memory and attention.
Semax peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.
1. A. Srivastava et al., Nootropic Phytomedicine. New Look to Phytomedicine, 2019. https://www.sciencedirect.com/topics/neuroscience/nootropic
2. T. Kolomin et al., A New Generation of Drugs: Synthetic Peptides based on Natural Regulatory peptides. Neuroscience & Medicine, 2013, 223-252. Published Online December 2013. http://dx.doi.org/10.4236/nm.2013.44035
3. Dornbush RL, Nikolovski O. ACTH 4-10 and short-term memory. Pharmacol Biochem Behav. 1976;5(Suppl 1):69-72. doi: 10.1016/0091-3057(76)90331-2. PMID: 189333. https://pubmed.ncbi.nlm.nih.gov/189333/
4. Essential Medicines and Health Products Information Portal, A World Health Organization resource.
5. U.S. Food and Drug Administration, Drug databases.
6. Kost NV, Sokolov OIu, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, Zozulia AA. Ingibiruiushchee deĭstvie semaksa i selanka na énkefalindegradiruiushchie fermenty syvorotki krovi cheloveka [Semax and selank inhibit the enkephalin-degrading enzymes from human serum]]. Bioorg Khim. 2001 May-Jun;27(3):180-3. Russian. doi: 10.1023/a:1011373002885. PMID: 11443939. https://pubmed.ncbi.nlm.nih.gov/11443939/
7. Shih-Jen Tsai, Semax, an analogue of adrenocorticotropin (4–10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome, Medical Hypotheses, Volume 68, Issue 5, 2007, Pages 1144-1146. https://doi.org/10.1016/j.mehy.2006.07.017
8. Medvedeva, E.V., Dmitrieva, V.G., Povarova, O.V. et al. 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 (2014). https://doi.org/10.1186/1471-2164-15-228
9. 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.
10. Nataliya Yu. Glazova, Daria M. Manchenko, Maria A. Volodina, Svetlana A. Merchieva, Ludmila A. Andreeva, Vladimir S. Kudrin, Nikolai F. Myasoedov, Natalia G. Levitskaya, Semax, synthetic ACTH(4–10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats, Neuropeptides, Volume 86, 2021, 102114, ISSN 0143-4179. https://doi.org/10.1016/j.npep.2020.102114
11. Gavrilova SA, Golubeva AV, Lipina TV, Fominykh ES, Shornikova MV, Postnikov AB, Andrejeva LA, Chentsov IuS, Koshelev VB. [Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction]. Ross Fiziol Zh Im I M Sechenova. 2006 Nov;92(11):1305-21. Russian. PMID: 17385423. https://pubmed.ncbi.nlm.nih.gov/17385423/
12. Volodina MA, Sebentsova EA, Glazova NY, Levitskaya NG, Andreeva LA, Manchenko DM, Kamensky AA, Myasoedov NF. Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats. Bull Exp Biol Med. 2012 Mar;152(5):560-3. English, Russian. doi: 10.1007/s10517-012-1574-2. PMID: 22803132. https://pubmed.ncbi.nlm.nih.gov/22803132/
13. Gusev EI, Skvortsova VI, Miasoedov NF, Nezavibat’ko VN, Zhuravleva EIu, Vanichkin AV. 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)]. Zh Nevrol Psikhiatr Im S S Korsakova. 1997;97(6):26-34. Russian. PMID: 11517472. https://pubmed.ncbi.nlm.nih.gov/11517472/
14. Asmarin IP, Nezavibat’ko VN, Miasoedov NF, Kamenskiĭ AA, Grivennikov IA, Ponomareva-Stepnaia MA, Andreeva LA, Kaplan AIa, Koshelev VB, Riasina TV. Nootropnyĭ analog adrenokortikotropina 4-10-semaks (15-letniĭ opyt razrabotki i izucheniia) [A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study)]. Zh Vyssh Nerv Deiat Im I P Pavlova. 1997 Mar-Apr;47(2):420-30. Russian. PMID: 9173745. https://pubmed.ncbi.nlm.nih.gov/9173745/
15. Bobyntsev I, Kryukov AA, Shepeleva M, Ivanov AV. The Effect of Acth-(4-7)-Pgp Peptide On Lipid Peroxidation In Liver And Activity Of Serum Transaminases In Rats Under Acute And Chronic Immobilization Stress Conditions]. Eksp Klin Farmakol. 2015;78(8):18-21. Russian. PMID: 26591577. https://pubmed.ncbi.nlm.nih.gov/26591577/
NOTE: These products are intended for laboratory research use only. Semax for sale is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.
Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.