Chemistry:Semax
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| Trade names | Semax |
| Other names | L-Methionyl-L-α-glutamylhistidyl-L-phenylalanyl-L-prolylglycyl-L-proline, (Pro8,Gly9,Pro10)ACTH-(4-10) |
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| Formula | C37H51N9O10S |
| Molar mass | 813.93 g·mol−1 |
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Semax is a drug which is used mostly in Russia for a broad range of conditions but predominantly for its purported nootropic, neuroprotective, and neurorestorative properties. Semax has not been evaluated, approved for use, or marketed in most other countries. It is prescribed in eastern Europe and Russia for brain trauma.
Etymology
Semax is composed of seven amino acid residues: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP), which is reflected in the name - from an abbreviation of "Seven amino acids"- in Russian: СЕМь АминоКиСлот - СЕМАКС.
Marketing
Marketing Development and production: PEPTOGEN (Russian Federation) Joint-Stock Company «Innovative Research-and-Production Center «Peptogen» (JSC «Peptogen»), Russian Federation was founded in 2005 with the participation of the Institute of Molecular Genetics of the Russian Academy of Sciences
Medical uses
Semax has undergone extensive study in Russia and is on the Russian List of Vital & Essential Drugs approved by the Russian Federation government on December 7, 2011.[1] Medical uses for Semax include treatment of stroke, transient ischemic attack, memory and cognitive disorders, peptic ulcers, optic nerve disease, and to boost the immune system.[2][3][4][5]
Pharmacology
Pharmacodynamics
In animals, Semax rapidly elevates the levels and expression of brain-derived neurotrophic factor (BDNF) and its signaling receptor TrkB in the hippocampus,[6] and rapidly activates serotonergic and dopaminergic brain systems.[7][8] Accordingly, it has been found to produce antidepressant-like and anxiolytic-like effects,[9][10] attenuate the behavioral effects of exposure to chronic stress,[9][10] and potentiate the locomotor activity produced by D-amphetamine.[8][11] As such, it has been suggested that Semax may be effective in the treatment of depression.[12]
Though the exact mechanism of action of Semax is unclear, there is evidence that it may act through melanocortin receptors. Specifically, there is a report of Semax competitively antagonizing the action of the melanocortin receptor full agonist α-melanocyte-stimulating hormone (α-MSH) at the MC4 and MC5 receptors in both in vitro and in vivo experimental conditions, indicating that it may act as an antagonist or partial agonist of these receptors.[13] Semax did not antagonize α-MSH at the MC3 receptor, though this receptor could still be a target of the drug.[13] As for the MC1 and MC2 receptors, they were not assayed.[13] In addition to actions at receptors, Semax, as well as a related peptide drug, Selank, have been found to inhibit enzymes involved in the degradation of enkephalins and other endogenous regulatory peptides (IC50 = 10 μM), though the clinical significance of this property is uncertain.[14]
Pharmacokinetics
As a peptide, Semax has poor oral bioavailability and hence is administered parenterally as a nasal spray or subcutaneous injection.
Human trials
In a 2018 study involving 24 healthy participants, Semax was shown to increase fMRI default mode network activity relative to placebo.[15]
In an earlier 1996 study, 250-1000 ug/kg of Semax improved attention and short term memory in 11 healthy subjects performing 8 hour work shifts, though the effects were most pronounced when subjects were fatigued (after the shift was over) and the effects lasted going into the next day.[16] In a follow-up memory test administered the morning after Semax administration, the treatment group made more correct responses (71%) than the control group (41%).[16]
A study involving 110 patients recovering from ischemic stroke reported increases in BDNF (correlated with early rehabilitation) in patients administered Semax.[17]
As of November 2023, there are no published human trials involving Semax outside of Russia and Post-Soviet states.[18]
Chemistry
Semax is a heptapeptide and synthetic analogue of a fragment of adrenocorticotropic hormone (ACTH), ACTH (4-10), of the following amino acid sequence: Met-Glu-His-Phe-Pro-Gly-Pro (MEHFPGP in single-letter form).
References
- ↑ "ПЕРЕЧЕНЬ. жизненно необходимых и важнейших лекарственных препаратов на 2012 год. (Vital and Essential Drugs List, 2012) - Russian Federation". World Health Organization. 2012. http://apps.who.int/medicinedocs/en/d/Js19766ru/.
- ↑ "Semax". Institute of Molecular Genetics, Russian Academy of Sciences. http://old.img.ras.ru/semax1-e.htm.
- ↑ "[Semax in the treatment of glaucomatous optic neuropathy in patients with normalized ophthalmic tone]". Vestnik Oftalmologii 117 (4): 5–8. 2001. PMID 11569188.
- ↑ "Therapy of peptic ulcer with semax peptide". Bulletin of Experimental Biology and Medicine 134 (1): 73–74. July 2002. doi:10.1023/A:1020621124776. PMID 12459874.
- ↑ "Current approaches to the analysis of the effects of stress on metabolic processes in cells of the nervous and immune systems". Med. Immunology 1 (1–2): 17–22. 1999.
- ↑ "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. October 2006. doi:10.1016/j.brainres.2006.07.108. PMID 16996037.
- ↑ "Effects of Semax on dopaminergic and serotoninergic systems of the brain". Doklady Biological Sciences 394 (1–6): 1–3. 2004. doi:10.1023/b:dobs.0000017114.24474.40. PMID 15088389.
- ↑ 8.0 8.1 "Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents". Neurochemical Research 30 (12): 1493–1500. December 2005. doi:10.1007/s11064-005-8826-8. PMID 16362768.
- ↑ 9.0 9.1 "[Effects of chronic Semax administration on exploratory activity and emotional reaction in white rats]" (in ru). Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova 93 (6): 661–669. June 2007. PMID 17850024.
- ↑ 10.0 10.1 "Heptapeptide semax attenuates the effects of chronic unpredictable stress in rats". Doklady Biological Sciences 453: 353–357. November 2013. doi:10.1134/S0012496613060161. PMID 24385169.
- ↑ "Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats". Bulletin of Experimental Biology and Medicine 152 (5): 560–563. March 2012. doi:10.1007/s10517-012-1574-2. PMID 22803132.
- ↑ "Therapeutic possibility of "Semax" for depression". CNS Spectrums 13 (1): 20–21. January 2008. doi:10.1017/S1092852900016102. PMID 18204410.
- ↑ 13.0 13.1 13.2 "Drug-induced activation of the nervous control of inflammation: a novel possibility for the treatment of hypoxic damage". European Journal of Pharmacology 679 (1–3): 1–8. March 2012. doi:10.1016/j.ejphar.2012.01.004. PMID 22293371.
- ↑ "Semax and selank inhibit the enkephalin-degrading enzymes from human serum" (in ru). Bioorganicheskaia Khimiia 27 (3): 180–183. 2001. doi:10.1023/A:1011373002885. PMID 11443939.
- ↑ "Effects of Semax on the Default Mode Network of the Brain". Bulletin of Experimental Biology and Medicine 165 (5): 653–656. September 2018. doi:10.1007/s10517-018-4234-3. PMID 30225715.
- ↑ 16.0 16.1 "Synthetic acth analogue semax displays nootropic-like activity in humans.". Neuroscience Research Communications 19 (2): 115–123. September 1996. doi:10.1002/(SICI)1520-6769(199609)19:2<115::AID-NRC171>3.0.CO;2-B.
- ↑ "[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. 2018. doi:10.17116/jnevro20181183261-68. PMID 29798983.
- ↑ "Semax - Search Results - PubMed" (in en). https://pubmed.ncbi.nlm.nih.gov/?term=Semax&filter=pubt.clinicaltrial&filter=pubt.meta-analysis&filter=pubt.randomizedcontrolledtrial.
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