Chemistry:N-Phenylacetyl-L-prolylglycine ethyl ester

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Short description: Prodrug


N-Phenylacetyl-L-prolylglycine ethyl ester
Noopept.svg
Noopept.png
Clinical data
Trade namesNoopept
Other namesomberacetam; GVS-111; DVD-111; SGS-111; benzylcarbonyl-Pro-Gly-OEt
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: Unapproved "New Drug" (as defined by 21 U.S. Code § 321(p)(1)). Use in dietary supplements, food, or medicine is unlawful; otherwise uncontrolled.
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC17H22N2O4
Molar mass318.373 g·mol−1
3D model (JSmol)
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N-Phenylacetyl-l-prolylglycine ethyl ester is promoted as a nootropic and is a prodrug of cyclic glycine-proline.[lower-alpha 1][2] Other names include the brand name Noopept (Russian: Ноопепт), developmental code GVS-111; proposed INN omberacetam.[2][3][4]

Its synthesis was first reported in 1996.[2] It is orally available, as of 2017 its metabolism and elimination half-life were not well understood, and cycloprolylglycine has not been measured in humans following administration.[2] In cell culture, cycloprolylglycine increases brain derived neurotrophic factor (BDNF).[5]

It has been evaluated for neuroprotective effects in treating brain injuries and stroke.[6]

Pharmacology

One oft-cited study (originally published in Russian) conducted on rats, suggests that Noopept works via the "antioxidant effect, the anti-inflammatory action, and the ability to inhibit the neurotoxicity of excess calcium and glutamate, and to improve the blood rheology".[6]

Some studies suggest that the pharmacological properties of Noopept are derived from its action as an activator of Hypoxia-inducible factor (HIF-1).[7][8]

Analysis of the active site of prolyl hydroxylase enzyme 2. A – active center occupied by "native" ligand. B – interaction between inhibitor and amino acid residues of the enzyme (docking solution)
Molecular Docking – Depiction of noopept binding to prolyl hydroxilase enzymes, hence preventing the breakdown of HIF-1 which takes place under normal oxygenation conditions.

Most of the effects of Noopept could be explained by its action as an activator of HIF-1.[8]

Dosage

Noopept is frequently dosed at 10-30mg per day. However, there is no solid evidence indicating that any dose of Noopept is optimal. Few human trials have ever been carried out on Noopept, and as one meta-analysis notes, animal studies have used doses ranging from 0.1mg/kg bodyweight to 10mg/kg bodyweight.[unreliable medical source?][9] Furthermore, no long-term studies have been done to evaluate the lasting effects of chronic use at any given dose; the longest human study lasted for 56 days.[10] There is, therefore, no dose of Noopept which may be called "safe".

Legal status

  • Hungary: As of 25 August 2020, Noopept is added to the controlled psychoactive substances list, prohibiting production, sale, import, storage and use.[11]
  • Russia: Noopept in Russia is a drug of medicine and is available without a prescription.[12]
  • United Kingdom: Contrary to popular belief, omberacetam is not illegal to produce, supply, or import under the Psychoactive Substance Act in the UK, which came into effect on May 26, 2016 because it does neither work as a CNS (central nervous system) depressant, nor as a CNS stimulant.[13] However, sale and supply for human consumption are prohibited.
  • United States: The Food and Drug Administration has issued import alerts for imports of omberacetam, considering it an analog of piracetam.[14] FDA considers such racetam-family substances Active Pharmaceutical Ingredients (APIs) that require new drug applications and adequate labelling before being imported.[15] Similarly, warnings have been issued for claims of medical and pharmacological effects.[16] Despite these FDA enforcement actions, omberacetam is sold in over-the-counter supplements in this US with some products formulated with dosages greater than pharmaceutical levels.[17]

See also

Notes

  1. ↑ Referring to the cyclic dipeptide better known as cyclo(prolylglycyl), i.e. (S)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione.[1] Not to be confused with a cyclopropanyl moiety.

References

  1. ↑ "Omberacetam". Inxight. National Center for Advancing Translational Sciences (NCATS). https://drugs.ncats.io/drug/4QBJ98683M. 
  2. ↑ 2.0 2.1 2.2 2.3 "Noopept Information". Examine.com. http://examine.com/supplements/Noopept/. 
  3. ↑ "Proposed INN List 117". WHO Drug Information 31 (2): 308. 2017. https://www.who.int/publications/m/item/inn-pl-117. 
  4. ↑ "Omberacetam" (in en). AdisInsight. Springer Nature Switzerland AG. https://adisinsight.springer.com/drugs/800006775. "Alternative Names: DVD-111; GVS 111; Noopept" 
  5. ↑ "Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells". Doklady. Biochemistry and Biophysics 469 (1): 273–276. July 2016. doi:10.1134/S1607672916040104. PMID 27599510. 
  6. ↑ 6.0 6.1 "[The original novel nootropic and neuroprotective agent noopept]" (in Russian). Eksperimental'naia i Klinicheskaia Farmakologiia 65 (5): 66–72. 2002. PMID 12596521. 
  7. ↑ "Cognitive Enhancer Noopept Activates Transcription Factor HIF-1". Doklady. Biochemistry and Biophysics 494 (1): 256–260. September 2020. doi:10.1134/S1607672920050129. PMID 33119829. 
  8. ↑ 8.0 8.1 "Molecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept". Acta Naturae 8 (1): 82–89. 2016. doi:10.32607/20758251-2016-8-1-82-89. PMID 27099787. 
  9. ↑ "Finding the optimal dosage fornootropic agent Noopept: An analysis of available literature". International Journal of Environmental Science and Technology. 2020. http://ijest.org/Noopept_Dosage_PTardner1120.pdf. 
  10. ↑ "Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin". Neuroscience and Behavioral Physiology 39 (3): 311–321. March 2009. doi:10.1007/s11055-009-9128-4. PMID 19234797. 
  11. ↑ "Az új pszichoaktív anyaggá minősített anyagokról vagy vegyületcsoportokról szóló 55/2014. (XII. 30.) EMMI rendelet módosításáról" (in Hungarian). Magyarország Hivatalos Lapja 194: 6135–6142 (6139). 25 August 2020. https://magyarkozlony.hu/hivatalos-lapok/fsmDhb9y0CRKX2SkxRDw5f37b222dc2d1/dokumentumok/bc9ef7aef40a107a518ab17e1ac35adf2735e291/letoltes. Retrieved 28 April 2021. 
  12. ↑ "Ноопепт" (in Russian). Государственный реестр лекарственных средств. http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=6e1f901d-6924-4721-87d5-c82880be8286&t=. 
  13. ↑ "Psychoactive Substances Act 2016". Legislation.gov.uk. http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted. 
  14. ↑ "Presence of Piracetam in Cognitive Enhancement Dietary Supplements". JAMA Internal Medicine 180 (3): 458–459. March 2020. doi:10.1001/jamainternmed.2019.5507. PMID 31764936. 
  15. ↑ "Import alert 66-66". U.S. Food and Drug Administration. 7 September 2021. https://www.accessdata.fda.gov/cms_ia/importalert_202.html. 
  16. ↑ "Peak Nootropics LLC aka Advanced Nootropics". FDA Warning letter. U.S. Food and Drug Administration. 5 February 2019. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/peak-nootropics-llc-aka-advanced-nootropics-557887-02052019. 
  17. ↑ "Five Unapproved Drugs Found in Cognitive Enhancement Supplements". Neurology. Clinical Practice 11 (3): e303–e307. June 2021. doi:10.1212/CPJ.0000000000000960. PMID 34484905. 



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