N-Phenylacetyl-L-prolylglycine ethyl ester explained

Verifiedfields:	changed
Watchedfields:	changed
Verifiedrevid:	424810394
Drug Name:	N-Phenylacetyl-L-prolylglycine ethyl ester
Iupac Name:	Ethyl 1-(phenylacetyl)--prolylglycinate
Width:	220
Tradename:	Noopept
Legal Au:	S4
Legal 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.
Cas Number:	157115-85-0
Unii:	4QBJ98683M
Pubchem:	180496
Synonyms:	omberacetam; GVS-111; DVD-111; SGS-111; benzylcarbonyl-Pro-Gly-OEt
C:	17
H:	22
N:	2
O:	4
Smiles:	c2ccccc2CC(=O)N1CCC[C@@H]1C(=O)NCC(=O)OCC
Chemspiderid:	157065
Stdinchi:	1S/C17H22N2O4/c1-2-23-16(21)12-18-17(22)14-9-6-10-19(14)15(20)11-13-7-4-3-5-8-13/h3-5,7-8,14H,2,6,9-12H2,1H3,(H,18,22)/t14-/m0/s1
Stdinchikey:	PJNSMUBMSNAEEN-AWEZNQCLSA-N

N-Phenylacetyl--prolylglycine ethyl ester is promoted as a nootropic and is a prodrug of cyclic glycine-proline.^[1] Other names include the brand name Noopept (Russian: link=no|Ноопепт), developmental code GVS-111, and proposed INN omberacetam.^{[1] [2] [3]}

Its synthesis was first reported in 1996.^[1] 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.^[1] In cell culture, cycloprolylglycine increases brain derived neurotrophic factor (BDNF).^[4]

It has been evaluated for neuroprotective effects in treating brain injuries and stroke.^[5]

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".

Some studies suggest that the pharmacological properties of Noopept are derived from its action as an activator of Hypoxia-inducible factor (HIF-1).^{[6] [7]} Most of the effects of Noopept could be explained by its action as an activator of HIF-1.

Dosage

Noopept is frequently dosed at 10–30 mg 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 0.1 mg/kg bodyweight to 10 mg/kg bodyweight.^[8] 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.^[9] 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.^[10]
• Russia: Noopept in Russia is a drug of medicine and is available without a prescription.^[11]
• 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 neither works as a CNS (central nervous system) depressant, nor as a CNS stimulant.^[12] 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.^[13] FDA considers such racetam-family substances Active Pharmaceutical Ingredients (APIs) that require new drug applications and adequate labelling before being imported.^[14] Similarly, warnings have been issued for claims of medical and pharmacological effects.^[15] Despite these FDA enforcement actions, omberacetam is sold in over-the-counter supplements in the US, with some products formulated with dosages greater than pharmaceutical levels.^[16]

See also

• Modafinil
• Nootropic
• Stimulant

Notes and References

1. Web site: Noopept Information. Examine.com. 6 April 2017.
2. Proposed INN List 117. WHO Drug Information. 2017. 31. 2. 308.
3. Web site: Omberacetam . Alternative Names: DVD-111; GVS 111; Noopept . AdisInsight . Springer Nature Switzerland AG . 12 May 2018. en.
4. Gudasheva TA, Koliasnikova KN, Antipova TA, Seredenin SB . Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells . Doklady. Biochemistry and Biophysics . 469 . 1 . 273–276 . July 2016 . 27599510 . 10.1134/S1607672916040104 . 254426990 .
5. Ostrovskaia RU, Gudasheva TA, Voronina TA, Seredenin SB . [The original novel nootropic and neuroprotective agent noopept] . Russian . Eksperimental'naia i Klinicheskaia Farmakologiia . 65 . 5 . 66–72 . 2002 . 12596521 . Experimental and Clinical Pharmacology . The original novel nootropic and neuroprotective agent noopept .
6. Zainullina LF, Ivanova TV, Sadovnikov SV, Vakhitova YV, Seredenin SB . Cognitive Enhancer Noopept Activates Transcription Factor HIF-1 . Doklady. Biochemistry and Biophysics . 494 . 1 . 256–260 . September 2020 . 33119829 . 10.1134/S1607672920050129 . 226207175 .
7. Vakhitova YV, Sadovnikov SV, Borisevich SS, Ostrovskaya RU, A Gudasheva T, Seredenin SB . Molecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept . Acta Naturae . 8 . 1 . 82–89 . 2016 . 27099787 . 4837574 . 10.32607/20758251-2016-8-1-82-89 .
8. Tardner P . 2020. Finding the optimal dosage fornootropic agent Noopept: An analysis of available literature. International Journal of Environmental Science and Technology.
9. Neznamov GG, Teleshova ES . 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 . 19234797 . 10.1007/s11055-009-9128-4 . 3348153 .
10. Miklós K . 25 August 2020 . 194 . 6135–6142 (6139) . Az új pszichoaktív anyaggá minősített anyagokról vagy vegyületcsoportokról szóló 55/2014. (XII. 30.) EMMI rendelet módosításáról . About substances classified as new psychoactive substances or 55/2014 on groups of compounds (XII. 30.) amending the EMMI Decree . Magyarország Hivatalos Lapja . Official Journal of Hungry . Hungarian . 28 April 2021 .
11. Web site: Ноопепт . Noopept . Государственный реестр лекарственных средств . State Register of Medicines . Russian .
12. Web site: Psychoactive Substances Act 2016 . Legislation.gov.uk .
13. Cohen PA, Zakharevich I, Gerona R . Presence of Piracetam in Cognitive Enhancement Dietary Supplements . JAMA Internal Medicine . 180 . 3 . 458–459 . March 2020 . 31764936 . 6902196 . 10.1001/jamainternmed.2019.5507 .
14. Web site: Import alert 66-66 . U.S. Food and Drug Administration . 7 September 2021 .
15. Web site: Peak Nootropics LLC aka Advanced Nootropics . FDA Warning letter . 5 February 2019 . U.S. Food and Drug Administration . Correll Jr WA .
16. Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I . Five Unapproved Drugs Found in Cognitive Enhancement Supplements . Neurology. Clinical Practice . 11 . 3 . e303–e307 . June 2021 . 34484905 . 8382366 . 10.1212/CPJ.0000000000000960 .