Semax

Last updated

Semax
Semax.svg
Clinical data
Trade names Semax
Other namesL-Methionyl-L-α-glutamylhistidyl-L-phenylalanyl-L-prolylglycyl-L-proline, (Pro8,Gly9,Pro10)ACTH-(4-10)
ATC code
Legal status
Legal status
  • US:Not FDA approved; unscheduled
Identifiers
  • (2S)-1-[2-{[(2S)-1-[(2S)-2-{[2-{[(2S)-2-{[(2S)-2-amino-4-methylsulfanylbutanoyl]amino}-4-carboxybutanoyl]amino}-3-(1H-imidazol-5-yl)propanoyl]amino}-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino}acetyl]pyrrolidine-2-carboxylic acid
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C37H51N9O10S
Molar mass 813.93 g·mol−1
3D model (JSmol)
  • O=C(N[C@@H](CCC(O)=O)C(N[C@@H](CC1=CNC=N1)C(N[C@@H](CC2=CC=CC=C2)C(N3[C@@H](CCC3)C(NCC(N4[C@@H](CCC4)C(O)=O)=O)=O)=O)=O)=O)[C@H](CCSC)N
  • InChI=1S/C37H51N9O10S/c1-57-16-13-24(38)32(50)42-25(11-12-31(48)49)33(51)43-26(18-23-19-39-21-41-23)34(52)44-27(17-22-7-3-2-4-8-22)36(54)46-15-5-9-28(46)35(53)40-20-30(47)45-14-6-10-29(45)37(55)56/h2-4,7-8,19,21,24-29H,5-6,9-18,20,38H2,1H3,(H,39,41)(H,40,53)(H,42,50)(H,43,51)(H,44,52)(H,48,49)(H,55,56)/t24-,25-,26?,27-,28-,29-/m0/s1
  • Key:AFEHBIGDWIGTEH-CXFOGXNKSA-N

Semax is a medication which is used in Russia and Eastern Europe for the treatment of a broad range of conditions like brain trauma but predominantly for its claimed nootropic, neuroprotective, and neurorestorative effects. [1]

Contents

The mechanism of action of Semax is unknown. [2] [3] It might interact with certain melanocortin receptors or inhibit enkephalinase enzymes. [2] [3] Chemically, Semax is a peptide and a synthetic analogue of a fragment of adrenocorticotropic hormone (ACTH). [4] [5]

Semax was first described by 1991. [5] Although used as a prescription drug in Russia and Eastern Europe, Semax has not been evaluated, approved for use, or marketed in most other countries. [6] [7] The drug is widely sold by online vendors and used as a purported nootropic (cognitive enhancer). [1] [8]

Medical uses

Semax 1% from Russia. Semax 1%25 from Russia.jpg
Semax 1% from Russia.

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. [9] 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. [10] [11] [12] [13]

Clinical trials

In a 1996 study, 250 to 1000 μg 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. [14] 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%). [14]

A 2018 study involving 110 patients recovering from ischemic stroke reported increases in brain-derived neurotrophic factor (BDNF) (correlated with early rehabilitation) in patients administered Semax. [15]

In another 2018 study involving 24 healthy participants, Semax was shown to increase fMRI default mode network activity relative to placebo. [16]

As of November 2023, there are no published clinical trials involving Semax outside of Russia and post-Soviet states. [7]

Pharmacology

Pharmacodynamics

In animals, Semax rapidly elevates the levels and expression of brain-derived neurotrophic factor (BDNF) and its signaling receptor tropomyosin receptor kinase B (TrkB) in the hippocampus, [17] and rapidly activates serotonergic and dopaminergic brain systems. [18] [19] Accordingly, it has been found to produce antidepressant-like and anxiolytic-like effects, [20] [21] attenuate the behavioral effects of exposure to chronic stress, [20] [21] and potentiate the locomotor activity produced by D-amphetamine. [19] [22] As such, it has been suggested that Semax may be effective in the treatment of depression. [23]

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. [2] Semax did not antagonize α-MSH at the MC3 receptor, though this receptor could still be a target of the drug. [2] As for the MC1 and MC2 receptors, they were not assayed. [2] 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. [3]

Pharmacokinetics

As a peptide, Semax has poor oral bioavailability and hence is administered parenterally as a nasal spray or subcutaneous injection.

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). [4]

History

Semax was first described in the scientific literature by 1991. [5]

Society and culture

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

Semax was developed, produced, and marketed by Peptogen in the Russian Federation with participation of the Institute of Molecular Genetics of the Russian Academy of Sciences.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the zona fasiculata and zona reticularis, respectively. ACTH is also related to the circadian rhythm in many organisms.

The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating hormone (β-MSH), and γ-melanocyte-stimulating hormone (γ-MSH) that are produced by cells in the pars intermedia of the anterior lobe of the pituitary gland.

β-Carboline Chemical compound also known as norharmane

β-Carboline (9H-pyrido[3,4-b]indole) represents the basic chemical structure for more than one hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective substituent. Natural β-carbolines primarily influence brain functions but can also exhibit antioxidant effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-cancer properties.

<span class="mw-page-title-main">Piracetam</span> Chemical compound

Piracetam is a drug that has efficacy in cognitive disorders, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia; sources differ on its usefulness for dementia. Piracetam is sold as a medication in many European countries. Sale of piracetam is not illegal in the United States, although it is not regulated nor approved by the FDA, so it is legally sold for research use only.

<span class="mw-page-title-main">Phenylpiracetam</span> Chemical compound

Phenylpiracetam, also known as fonturacetam and sold under the brand names Phenotropil, Actitropil, and Carphedon among others, is a stimulant and nootropic medication used in Russia and certain other Eastern European countries in the treatment of cerebrovascular deficiency, depression, apathy, and attention, and memory problems, among other indications. It is also used in Russian cosmonauts to improve physical, mental, and cognitive abilities. The drug is taken by mouth.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.

Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors.

<span class="mw-page-title-main">Picamilon</span> Chemical compound

Picamilon is a drug formed by a synthetic combination of niacin and γ-aminobutyric acid (GABA). It was developed in the Soviet Union in 1969 and further studied in both Russia and Japan as a prodrug of GABA.

<span class="mw-page-title-main">ACTH receptor</span> Mammalian protein found in Homo sapiens

The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (type 2) which is specific for ACTH. A G protein–coupled receptor located on the external cell plasma membrane, it is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase. The ACTH receptor plays a role in immune function and glucose metabolism.

<span class="mw-page-title-main">Melanocortin 4 receptor</span> Mammalian protein found in Homo sapiens

Melanocortin 4 receptor (MC4R) is a melanocortin receptor that in humans is encoded by the MC4R gene. It encodes the MC4R protein, a G protein-coupled receptor (GPCR) that binds α-melanocyte stimulating hormone (α-MSH). In mouse models, MC4 receptors have been found to be involved in feeding behaviour, the regulation of metabolism, sexual behaviour, and male erectile function.

<span class="mw-page-title-main">Bromantane</span> Stimulant drug

Bromantane, sold under the brand name Ladasten, is an atypical central nervous system (CNS) stimulant and anxiolytic drug of the adamantane family that is related to amantadine and memantine. Medically, it is approved in Russia for the treatment of neurasthenia. Although the effects of bromantane have been determined to be dependent on the dopaminergic and possibly serotonergic neurotransmitter systems, its exact mechanism of action is unknown, and is distinct in its properties relative to typical stimulants such as amphetamine. Bromantane has sometimes been described as an actoprotector.

<i>N</i>-Phenylacetyl-<small>L</small>-prolylglycine ethyl ester Prodrug

N-Phenylacetyl-l-prolylglycine ethyl ester is promoted as a nootropic and is a prodrug of cyclic glycine-proline. Other names include the brand name Noopept, developmental code GVS-111, and proposed INN omberacetam.

<span class="mw-page-title-main">Sunifiram</span> Chemical compound

Sunifiram is an experimental drug which has antiamnesic effects in animal studies and with significantly higher potency than piracetam. Sunifiram is a molecular simplification of unifiram (DM-232). Another analogue is sapunifiram (MN-19). As of 2016, sunifiram had not been subjected to toxicology testing, nor to any human clinical trials, and is not approved for use anywhere in the world.

<span class="mw-page-title-main">Fabomotizole</span> Anxiolytic drug

Fabomotizole is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions. Its mechanism of action remains poorly defined however, with GABAergic, NGF- and BDNF-release-promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma agonism suggested as potential mechanisms. Fabomotizole was shown to inhibit MAO-A reversibly and there might be also some involvement with serotonin receptors. Clinical trials have shown fabomotizole to be well tolerated and reasonably effective for the treatment of anxiety.

<span class="mw-page-title-main">Selank</span> Chemical compound

Selank is a nootropic, anxiolytic peptide based drug developed by the Institute of Molecular Genetics of the Russian Academy of Sciences. Selank is a heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro (TKPRPGP). It is a synthetic analogue of human tuftsin.

α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone and neuropeptide of the melanocortin family, with a tridecapeptide structure and the amino acid sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It is the most important of the melanocyte-stimulating hormones (MSHs) (also known as melanotropins) in stimulating melanogenesis, a process that in mammals (including humans) is responsible for pigmentation primarily of the hair and skin. It also plays a role in feeding behavior, energy homeostasis, sexual activity, and protection against ischemia and reperfusion injury.

<span class="mw-page-title-main">Neurobiological effects of physical exercise</span> Neural, cognitive, and behavioral effects of physical exercise

The neurobiological effects of physical exercise involve possible interrelated effects on brain structure, brain function, and cognition. Research in humans has demonstrated that consistent aerobic exercise may induce improvements in certain cognitive functions, neuroplasticity and behavioral plasticity; some of these long-term effects may include increased neuron growth, increased neurological activity, improved stress coping, enhanced cognitive control of behavior, improved declarative, spatial, and working memory, and structural and functional improvements in brain structures and pathways associated with cognitive control and memory. The effects of exercise on cognition may affect academic performance in children and college students, improve adult productivity, preserve cognitive function in old age, preventing or treating certain neurological disorders, and improving overall quality of life.

Cerebrolysin is an experimental mixture of enzymatically-treated peptides derived from pig brain whose constituents can include brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF). Although it is under preliminary study for its potential to treat various brain diseases, it is used as a therapy in dozens of countries in Eurasia.

Modimelanotide (INN) (code names AP-214, ABT-719, ZP-1480) is a melanocortinergic peptide drug derived from α-melanocyte-stimulating hormone (α-MSH) which was under development by, at different times, Action Pharma, Abbott Laboratories, AbbVie, and Zealand for the treatment of acute kidney injury. It acts as a non-selective melanocortin receptor agonist, with IC50 values of 2.9 nM, 1.9 nM, 3.7 nM, and 110 nM at the MC1, MC3, MC4, and MC5 receptors. Modimelanotide failed clinical trials for acute kidney injury despite showing efficacy in animal models, and development was not further pursued.

<span class="mw-page-title-main">BNN-20</span> Chemical compound

BNN-20, also known as 17β-spiro-(androst-5-en-17,2'-oxiran)-3β-ol, is a synthetic neurosteroid, "microneurotrophin", and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA). It acts as a selective, high-affinity, centrally active agonist of the TrkA, TrkB, and p75NTR, receptors for the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as for DHEA and DHEA sulfate (DHEA-S). The drug has been suggested as a potential novel treatment for Parkinson's disease and other conditions.

References

  1. 1 2 Voronina TA (2023). "Cognitive Impairment and Nootropic Drugs: Mechanism of Action and Spectrum of Effects". Neurochemical Journal. 17 (2): 180–188. doi: 10.1134/S1819712423020198 . ISSN   1819-7124.
  2. 1 2 3 4 5 Bertolini A (March 2012). "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. doi:10.1016/j.ejphar.2012.01.004. PMID   22293371.
  3. 1 2 3 Kost NV, Sokolov OI, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, et al. (2001). "Semax and selank inhibit the enkephalin-degrading enzymes from human serum". Bioorganicheskaia Khimiia (in Russian). 27 (3): 180–183. doi:10.1023/A:1011373002885. PMID   11443939. S2CID   26029820.
  4. 1 2 Deigin VI, Poluektova EA, Beniashvili AG, Kozin SA, Poluektov YM (March 2022). "Development of Peptide Biopharmaceuticals in Russia". Pharmaceutics. 14 (4): 716. doi: 10.3390/pharmaceutics14040716 . PMC   9030433 . PMID   35456550.
  5. 1 2 3 Potaman VN, Alfeeva LY, Kamensky AA, Levitzkaya NG, Nezavibatko VN (April 1991). "N-terminal degradation of ACTH(4-10) and its synthetic analog semax by the rat blood enzymes". Biochemical and Biophysical Research Communications. 176 (2): 741–746. doi:10.1016/S0006-291X(05)80247-5. PMID   1851003.
  6. ↑ "Home". AdisInsight. Retrieved 3 September 2024.
  7. 1 2 "Semax - Search Results - PubMed". PubMed. Retrieved 2023-11-12.
  8. ↑ Jędrejko K, Catlin O, Stewart T, Anderson A, Muszyńska B, Catlin DH (August 2023). "Unauthorized ingredients in "nootropic" dietary supplements: A review of the history, pharmacology, prevalence, international regulations, and potential as doping agents". Drug Testing and Analysis. 15 (8). Wiley: 803–839. doi:10.1002/dta.3529. PMID   37357012.
  9. ↑ "ПЕРЕЧЕНЬ. жизненно необходимых и важнейших лекарственных препаратов на 2012 год. (Vital and Essential Drugs List, 2012) - Russian Federation". World Health Organization. 2012. Archived from the original on February 2, 2015.
  10. ↑ "Semax". Institute of Molecular Genetics, Russian Academy of Sciences.
  11. ↑ Kurysheva NI, Shpak AA, Ioĭleva EE, Galanter LI, Nagornova ND, Shubina NI, et al. (2001). "[Semax in the treatment of glaucomatous optic neuropathy in patients with normalized ophthalmic tone]". Vestnik Oftalmologii. 117 (4): 5–8. PMID   11569188.
  12. ↑ Ivanikov IO, Brekhova ME, Samonina GE, Myasoedov NF, Ashmarin IP (July 2002). "Therapy of peptic ulcer with semax peptide". Bulletin of Experimental Biology and Medicine. 134 (1): 73–74. doi:10.1023/A:1020621124776. PMID   12459874. S2CID   23447014.
  13. ↑ Korneev EA, Kazakova TB (1999). "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.
  14. 1 2 Kaplan AY, Kochetova AG, Nezavibathko VN, Rjasina TV, Ashmarin IP (September 1996). "Synthetic acth analogue semax displays nootropic-like activity in humans". Neuroscience Research Communications. 19 (2): 115–123. doi:10.1002/(SICI)1520-6769(199609)19:2<115::AID-NRC171>3.0.CO;2-B.
  15. ↑ Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN (2018). "Éffektivnost' semaksa pri lechenii bol'nykh na raznykh stadiiakh ishemicheskogo insul'ta" [The efficacy of semax in the treatment of patients at different stages of ischemic stroke]. Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova. 118 (3. Vyp. 2): 61–68. doi: 10.17116/jnevro20181183261-68 . PMID   29798983.
  16. ↑ Lebedeva IS, Panikratova YR, Sokolov OY, Kupriyanov DA, Rumshiskaya AD, Kost NV, et al. (September 2018). "Effects of Semax on the Default Mode Network of the Brain". Bulletin of Experimental Biology and Medicine. 165 (5): 653–656. doi:10.1007/s10517-018-4234-3. PMID   30225715. S2CID   254292493.
  17. ↑ Dolotov OV, Karpenko EA, Inozemtseva LS, Seredenina TS, Levitskaya NG, Rozyczka J, et al. (October 2006). "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. doi:10.1016/j.brainres.2006.07.108. PMID   16996037. S2CID   27592503.
  18. ↑ Eremin KO, Kudrin VS, Grivennikov IA, Miasoedov NF, Rayevsky KS (2004). "Effects of Semax on dopaminergic and serotoninergic systems of the brain". Doklady Biological Sciences. 394 (1–6): 1–3. doi:10.1023/b:dobs.0000017114.24474.40. PMID   15088389. S2CID   12955434.
  19. 1 2 Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, et al. (December 2005). "Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents". Neurochemical Research. 30 (12): 1493–1500. doi:10.1007/s11064-005-8826-8. PMID   16362768. S2CID   38202287.
  20. 1 2 Vilenskiĭ DA, Levitskaia NG, Andreeva LA, Alfeeva LI, Kamenskiĭ AA, Miasoedov NF (June 2007). "[Effects of chronic Semax administration on exploratory activity and emotional reaction in white rats]". Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova (in Russian). 93 (6): 661–669. PMID   17850024.
  21. 1 2 Yatsenko KA, Glazova NY, Inozemtseva LS, Andreeva LA, Kamensky AA, Grivennikov IA, et al. (November 2013). "Heptapeptide semax attenuates the effects of chronic unpredictable stress in rats". Doklady Biological Sciences. 453: 353–357. doi:10.1134/S0012496613060161. PMID   24385169. S2CID   9699654.
  22. ↑ Volodina MA, Sebentsova EA, Glazova NY, Levitskaya NG, Andreeva LA, Manchenko DM, et al. (March 2012). "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. doi:10.1007/s10517-012-1574-2. PMID   22803132. S2CID   1419653.
  23. ↑ Pae CU (January 2008). "Therapeutic possibility of "Semax" for depression". CNS Spectrums. 13 (1): 20–21. doi: 10.1017/S1092852900016102 . PMID   18204410.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.