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 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.

Contents

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 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. [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).

Related Research Articles

Human enhancement is the natural, artificial, or technological alteration of the human body in order to enhance physical or mental capabilities.

<span class="mw-page-title-main">Vasopressin receptor 1B</span> Protein-coding gene in the species Homo sapiens

Vasopressin V1b receptor (V1BR) also known as vasopressin 3 receptor (VPR3) or antidiuretic hormone receptor 1B is a protein that in humans is encoded by the AVPR1B gene.

<span class="mw-page-title-main">Low-affinity nerve growth factor receptor</span> Human protein-coding gene

The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death.

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

<span class="mw-page-title-main">Corticotropin-like intermediate peptide</span> Chemical compound

Corticotropin-like intermediate [lobe] peptide (CLIP), also known as adrenocorticotropic hormone fragment 18-39, is a naturally occurring, endogenous neuropeptide with a docosapeptide structure and the amino acid sequence Arg-Pro-Val-Lys-Val-Tyr-Pro-Asn-Gly-Ala-Glu-Asp-Glu-Ser-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe. CLIP is generated as a proteolyic cleavage product of adrenocorticotropic hormone (ACTH), which in turn is a cleavage product of proopiomelanocortin (POMC). Its physiological role has been investigated in various tissues, specifically in the central nervous system.

An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor or leukotriene receptor antagonist and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in asthma and COPD. Leukotriene receptor antagonists are sometimes colloquially referred to as leukasts.

<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.

The glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms of schizophrenia linked to glutamatergic signaling. The hypothesis was initially based on a set of clinical, neuropathological, and, later, genetic findings pointing at a hypofunction of glutamatergic signaling via NMDA receptors. While thought to be more proximal to the root causes of schizophrenia, it does not negate the dopamine hypothesis, and the two may be ultimately brought together by circuit-based models. The development of the hypothesis allowed for the integration of the GABAergic and oscillatory abnormalities into the converging disease model and made it possible to discover the causes of some disruptions.

<span class="mw-page-title-main">LY-503430</span> Chemical compound

LY-503430 is an AMPA receptor positive allosteric modulator developed by Eli Lilly.

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

Bromantane, sold under the brand name Ladasten, is an atypical psychostimulant and anxiolytic drug of the adamantane family related to amantadine and memantine which is used in Russia in the treatment of neurasthenia. Although the effects of the bromantane have been determined to be dependent on the dopaminergic and possibly serotonergic neurotransmitter systems, its exact mechanism of action is unknown, and it is distinct in its properties relative to typical psychostimulants such as amphetamine. Because of its unique aspects, bromantane has sometimes been described instead as an adaptogen and actoprotector.

<span class="mw-page-title-main">A-77636</span> Chemical compound

A-77636 is a synthetic drug which acts as a selective D1 receptor full agonist. It has nootropic, anorectic, rewarding and antiparkinsonian effects in animal studies, but its high potency and long duration of action causes D1 receptor downregulation and tachyphylaxis, and unlike other D1 full agonists such as SKF-82,958, it does not produce place preference in animals. A-77636 partially substituted for cocaine in animal studies, and has been suggested for use as a possible substitute drug in treating addiction, but it is better known for its use in studying the role of D1 receptors in the brain.

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

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.

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

Repinotan (BAYx3702), an aminomethylchroman derivative, is a selective 5-HT1A receptor full agonist with high potency and efficacy. It has neuroprotective effects in animal studies, and was trialed in humans for reducing brain injury following head trauma. It was subsequently trialed up to phase II for treatment of stroke, but while side effects were mild and consisted mainly of nausea, repinotan failed to demonstrate sufficient efficacy to justify further clinical trials. However, repinotan continues to be investigated for other applications, and was found to be effective at counteracting the respiratory depression produced by morphine, though with slight reduction in analgesic effects.

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

Emoxypine (2-ethyl-6-methyl-3-hydroxypyridine), also known as Mexidol or Mexifin when used as the succinate salt, is an antioxidant actoprotector manufactured by Pharmasoft Pharmaceuticals. Its chemical structure resembles that of pyridoxine (a type of vitamin B6).

<span class="mw-page-title-main">S-18986</span> Chemical compound

S-18986 is a positive allosteric modulator of the AMPA receptor related to cyclothiazide. It has nootropic and neuroprotective effects in animal studies, and induces both production of BDNF and AMPA-mediated release of noradrenaline and acetylcholine in the hippocampus and frontal cortex of the brain.

<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.

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

Valorphin, also known as VV-hemorphin-5, is a naturally occurring, endogenous opioid heptapeptide of the hemorphin family with the amino acid sequence H-Val-Val-Tyr-Pro-Trp-Thr-Gln-OH (VVYPWTQ). It is produced in the body via proteolyic cleavage of residues 33-39 of the β-chain of hemoglobin. Valorphin binds preferentially to the μ-opioid receptor and produces effects such as analgesia and self-administration in animals. It also possesses cytotoxic and antiproliferative properties against tumor cells, the mediation of which, because they are reversed by naloxone, appears to be dependent on the opioid receptors.

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

Adapromine is an antiviral drug of the adamantane group related to amantadine (1-aminoadamantane), rimantadine, and memantine (1-amino-3,5-dimethyladamantane) that is marketed in Russia for the treatment and prevention of influenza. It is an alkyl analogue of rimantadine and is similar to rimantadine in its antiviral activity but possesses a broader spectrum of action, being effective against influenza viruses of both type A and B. Strains of type A influenza virus with resistance to adapromine and rimantadine and the related drug deitiforine were encountered in Mongolia and the Soviet Union in the 1980s.

<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. ↑ "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.
  2. ↑ "Semax". Institute of Molecular Genetics, Russian Academy of Sciences.
  3. ↑ Kurysheva NI, Shpak AA, Ioĭleva EE, Galanter LI, Nagornova ND, Shubina NI, Shlyshalova NN (2001). "[Semax in the treatment of glaucomatous optic neuropathy in patients with normalized ophthalmic tone]". Vestnik Oftalmologii. 117 (4): 5–8. PMID   11569188.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. 1 2 Eremin KO, Kudrin VS, Saransaari P, Oja SS, Grivennikov IA, Myasoedov NF, Rayevsky KS (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.
  9. 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.
  10. 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.
  11. ↑ 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.
  12. ↑ Pae CU (January 2008). "Therapeutic possibility of "Semax" for depression". CNS Spectrums. 13 (1): 20–21. doi: 10.1017/S1092852900016102 . PMID   18204410.
  13. 1 2 3 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.
  14. ↑ Kost NV, Sokolov OI, Gabaeva MV, Grivennikov IA, Andreeva LA, Miasoedov NF, Zozulia AA (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.
  15. ↑ Lebedeva IS, Panikratova YR, Sokolov OY, Kupriyanov DA, Rumshiskaya AD, Kost NV, Myasoedov NF (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.
  16. 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.
  17. ↑ Gusev EI, Martynov MY, Kostenko EV, Petrova LV, Bobyreva SN (2018). "[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. doi: 10.17116/jnevro20181183261-68 . PMID   29798983.
  18. ↑ "Semax - Search Results - PubMed". PubMed. Retrieved 2023-11-12.
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.