Pro-Gly-Pro-ACTH (4-7)

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Structural formula
Structural formula of Semax
General
Surname Pro-Gly-Pro-ACTH (4-7)
other names
  • Semax
  • L-methionyl-L-α-glutamylhistidyl-L-phenylalanyl-L-prolylglycyl-L-proline
  • Met-Glu-His-Phe-Pro-Gly-Pro
Molecular formula C 37 H 51 N 9 O 10 S
External identifiers / databases
CAS number 80714-61-0
PubChem 122178
Wikidata Q4415058
Drug information
ATC code

N06 BX

properties
Molar mass 813.92 g · mol -1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Pro-Gly-Pro-ACTH (4-7) is an organic compound belonging to the class of peptides . It is used in the form of a nasal solution (trade name Semax , Russian Семакс ) mainly in Russia and Ukraine for the treatment of various neurological disorders and diseases.

properties

The synthetically produced substance is chemically an analogue of the adrenocorticotropin fragment ACTH (4-10). The peptide (heptapeptide) made up of seven amino acids has the sequence and is said to have a nootropic and neuroprotective effect, but without being hormonally active. Met-Glu-His-Phe-Pro-Gly-Pro

Comparison of the amino acid sequences of ACTH (4-10) and the
synthetic heptapeptide Pro-Gly-Pro-ACTH (4-7): 
                           4   5   6   7   8   9   10
Fragment ACTH (4-10):     Met-Glu-His-Phe-Arg-Trp-Gly
Pro-Gly-Pro-ACTH (4-7):   Met-Glu-His-Phe-Pro-Gly-Pro

application areas

Semax was clinically developed in Russia and received drug approval in December 2011; Areas of application are the treatment of stroke in the acute phase, the treatment of neurological disorders after cerebral vascular injuries, transient ischemic attacks , arteriosclerotic encephalopathies and for recovery after a stroke , further improving the adaptability of the human body in extreme situations and preventing mental fatigue in monotonous work under stressful working conditions . In Russia , Semax is also used in ophthalmology for diseases of the optic nerve ( optic atrophy , inflammation of toxic or allergic origin) and in paediatrics for the treatment of attention deficit / hyperactivity disorder (ADHD). Possible areas of application also described in the literature are the treatment of gastric ulcers and the strengthening of the immune system .

Pro-Gly-Pro-ACTH (4-7) or methionyl-glutamyl-histidyl-phenylalanyl-prolyl-glycyl-prolin has been on a "list of essential and vital active ingredients" in Russia since December 2013.

There are no drug approvals in the USA, Canada and EU countries.

Pharmacokinetics

After application to the nasal mucous membrane, 60 to 70% of Pro-Gly-Pro-ACTH (4-7) is absorbed and is rapidly distributed in the blood and tissue. The active ingredient penetrates the blood-brain barrier . After systemic injection, the active ingredient is rapidly biotransformed and excreted in the urine. A prolonged effectiveness compared to that of the adrenocorticotropin fragment ACTH (4-10) arises from the fact that the C-terminal amino acid sequence Pro-Gly-Pro delays the enzymatic breakdown of the heptapeptide.

Studies

In animals, Pro-Gly-Pro-ACTH (4-7) increases gene expression and thus the concentration of the growth factor BDNF and its receptor TrkB in the hippocampus , which activates serotonergic and dopaminergic nerve cells. It therefore acts similarly to antidepressants and anxiolytics , reduces the effects of chronic stress on behavior and presumably increases the locomotor activity of D- amphetamine . Therefore, the use of Semax in the treatment of depression and attention deficit / hyperactivity disorder (ADHD) has been suggested.

Pro-Gly-Pro-ACTH (4-7), as well as a similar peptide active ingredient, Selank , suppresses various enzymes that are involved in the degradation of enkephalins and other endogenous regulating peptides .

Individual evidence

  1. ↑ a b Datasheet Semax, ≥98% (HPLC) from Sigma-Aldrich , accessed on January 28, 2015 ( PDF ).
  2. ↑ a b Vidal drug directory for Russia
  3. ↑ Instructions for use Semax 1%
  4. ↑ a b c Instructions for use Semax 0.1%
  5. ↑ NI Kurysheva, AA Shpak, EE Ioĭleva, LI Galanter, ND Nagornova, NIu Shubina, NN Shlyshalova: Semax in the treatment of glaucomatous optic neuropathy in patients with normalized ophthalmic tone . In: Vestnik oftalmologii . 117, No. 4, 2001, pp. 5-8. PMID 11569188 .
  6. ↑ IO Ivanikov, ME Brekhova, GE Samonina, NF Myasoedov, IP Ashmarin: Therapy of peptic ulcer with semax peptide . In: Bulletin of experimental biology and medicine . 134, No. 1, 2002, pp. 73-4. doi : 10.1023 / A: 1020621124776 . PMID 12459874 .
  7. ↑ Korneev, TB Kazakova: Current approaches to the analysis of the effects of stress on metabolic processes in cells of the nervous and immune systems . In: Med. Immunology . 1, No. 1-2, 1999, pp. 17-22.
  8. ↑ List of essential and vital medicines in accordance with Regulation 2199-p of the Government of the Russian Federation of December 7, 2012 ( Memento of the original of March 4, 2016 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , Page 80 @1@ 2Template: Webachiv / IABot / semax.ru
  9. ↑ OV Dolotov, EA Karpenko, LS Inozemtseva, et al .: Semax, an analog of ACTH (4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus . In: Brain Res. . 1117, No. 1, October 2006, pp. 54-60. doi : 10.1016 / j.brainres . 2006.07.108 . PMID 16996037 .
  10. ↑ KO Eremin, VS Kudrin, IA Grivennikov, NF Miasoedov, KS Rayevsky: Effects of Semax on dopaminergic and serotoninergic systems of the brain . In: Dokl. Biol. Sci. . 394, 2004, pp. 1-3. PMID 15088389 .
  11. ↑ a b K. O. Eremin, VS Kudrin, P. Saransaari, et al .: Semax, an ACTH (4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents . In: Neurochem. Res. . 30, No. 12, December 2005, pp. 1493-1500. doi : 10.1007 / s11064-005-8826-8 . PMID 16362768 .
  12. ^ A b D. A. Vilenskiĭ, NG Levitskaia, LA Andreeva, LI Alfeevau, AA Kamenskiĭ, NF Miasoedov: [Effects of chronic Semax administration on exploratory activity and emotional reaction in white rats] . In: Ross Fiziol Zh Im IM Sechenova . 93, No. 6, June 2007, pp. 661-9. PMID 17850024 .
  13. ↑ a b K. A. Yatsenko, NY Glazova, LS Inozemtseva, et al .: Heptapeptide semax attenuates the effects of chronic unpredictable stress in rats . In: Dokl. Biol. Sci. . 453, November 2013, pp. 353-357. doi : 10.1134 / S0012496613060161 . PMID 24385169 .
  14. ↑ MA Volodina, EA Sebentsova, NY Glazova, et al .: Semax Attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats . In: ... Bull Exp Biol Med. . 152, No. 5, March 2012, pp. 560-3. PMID 22803132 .
  15. ↑ Pae CU: Therapeutic possibility of "Semax" for depression . In: CNS Spectr . 13, No. 1, January 2008, pp. 20-21. PMID 18204410 .
  16. ↑ SJ Tsai: Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome . In: Med. Hypotheses . 68, No. 5, 2007, pp. 1144-1146. doi : 10.1016 / j.mehy.2006.07.017 . PMID 16996699 .
  17. ↑ NV food, OI Sokolovu, MV Gabaeva, et al .: Semax and selank inhibit the enkephalin-degrading enzymes from human serum . In: Bioorg. Khim. . 27, No. 3, 2001, pp. 180-183. PMID 11443939 .