N-Phenylacetyl-L-prolylglycine ethyl ester: Difference between revisions

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I added a much needed section on the side effects of Noopept. I also expanded on the liekly mechanism of action of the drug.
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==Pharmacology==
==Pharmacology==
Omberacetam modulates the [[acetylcholine]] system as well as the [[AMPA]] [[Receptor (biochemistry)|receptor]]s.<ref>{{cite journal | vauthors = Ostrovskaia RU, Gudasheva TA, Voronina TA, Seredenin SB | title = [The original novel nootropic and neuroprotective agent noopept] | journal = Eksperimental'naia i Klinicheskaia Farmakologiia | volume = 65 | issue = 5 | pages = 66–72 | date = September 2002 | pmid = 12596521 }}</ref> This modulation essentially allows acetylcholine to accumulate at higher levels than is typical. As acetylcholine is involved in the function of memory, this could potentially account for its [[nootropic]] effects. Some research also suggests that NMDA receptors are involved in omberacetam's mechanism of action.<ref name="pmid11177296">{{cite journal | vauthors = Andreeva NA, Stel'mashuk EV, Isaev NK, Ostrovskaya RU, Gudasheva TA, Viktorov IV | title = Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose deprivation, glutamate toxicity and oxidative stress | journal = Bulletin of Experimental Biology and Medicine | volume = 130 | issue = 10 | pages = 969–72 | date = October 2000 | pmid = 11177296 | doi = 10.1007/BF02682041| s2cid = 20572688 }}</ref><ref>{{cite journal | vauthors = Kovalev GI, Vorob'ev VV, Akhmetova ER | title = NMDA component in the effects of piracetam and new nootropic peptide GVS-111 on the neocortical and hippocampal EEG in conscious rats. | journal = Bulletin of Experimental Biology and Medicine. | date = August 1999 | volume = 128 | issue = 2 | pages = 822–5 | doi = 10.1007/BF02433825 | s2cid = 20090927 }}</ref>
Omberacetam modulates the [[acetylcholine]] system as well as the [[AMPA]] [[Receptor (biochemistry)|receptor]]s.<ref>{{cite journal | vauthors = Ostrovskaia RU, Gudasheva TA, Voronina TA, Seredenin SB | title = [The original novel nootropic and neuroprotective agent noopept] | journal = Eksperimental'naia i Klinicheskaia Farmakologiia | volume = 65 | issue = 5 | pages = 66–72 | date = September 2002 | pmid = 12596521 }}</ref> This modulation essentially allows acetylcholine to accumulate at higher levels than is typical. As acetylcholine is involved in the function of memory, this could potentially account for its [[nootropic]] effects. Some research also suggests that NMDA receptors are involved in omberacetam's mechanism of action.<ref name="pmid11177296">{{cite journal | vauthors = Andreeva NA, Stel'mashuk EV, Isaev NK, Ostrovskaya RU, Gudasheva TA, Viktorov IV | title = Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose deprivation, glutamate toxicity and oxidative stress | journal = Bulletin of Experimental Biology and Medicine | volume = 130 | issue = 10 | pages = 969–72 | date = October 2000 | pmid = 11177296 | doi = 10.1007/BF02682041| s2cid = 20572688 }}</ref><ref>{{cite journal | vauthors = Kovalev GI, Vorob'ev VV, Akhmetova ER | title = NMDA component in the effects of piracetam and new nootropic peptide GVS-111 on the neocortical and hippocampal EEG in conscious rats. | journal = Bulletin of Experimental Biology and Medicine. | date = August 1999 | volume = 128 | issue = 2 | pages = 822–5 | doi = 10.1007/BF02433825 | s2cid = 20090927 }}</ref>

Another probably mechanism of action of Noopept is neurotrophic factor expression stimulation. Animal studies show that Noopept consumption stimulates the production of both Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in rodent brains<ref>{{Cite journal|last=Ostrovskaya|first=R. U.|last2=Gudasheva|first2=T. A.|last3=Zaplina|first3=A. P.|last4=Vahitova|first4=Ju V.|last5=Salimgareeva|first5=M. H.|last6=Jamidanov|first6=R. S.|last7=Seredenin|first7=S. B.|date=2008-09|title=Noopept stimulates the expression of NGF and BDNF in rat hippocampus|url=https://pubmed.ncbi.nlm.nih.gov/19240853/|journal=Bulletin of Experimental Biology and Medicine|volume=146|issue=3|pages=334–337|doi=10.1007/s10517-008-0297-x|issn=0007-4888|pmid=19240853}}</ref>. While the effect appears to be reliable and significant across animal studies, no such studies have been carried out on humans. As such, this remains a speculative explanation for the observed nootropic effects of Noopept.

== Side effects ==
Noopept has been known to cause side effects in a significant number of users. While these side effects are typically mild and transient at doses around 10mg per day, both the chances and severity of side effects increases as doses approach 20mg per day and upward<ref>{{Cite journal|last=Tardner|first=Paul|date=|title=Finding the optimal dosage for nootropic agent Noopept: An analysis of available literature|url=http://ijest.org/Noopept_Dosage_PTardner1120.pdf|journal=International Journal of Environmental Science and Technology|volume=|pages=|via=}}</ref>. Side effects reported in clinical data collected on humans, as well as in anecdotal reports, include:

* Headaches
* Irritability<ref name=":0">{{Cite journal|last=Neznamov|first=G. G.|last2=Teleshova|first2=E. S.|date=2009-03|title=Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin|url=https://pubmed.ncbi.nlm.nih.gov/19234797/|journal=Neuroscience and Behavioral Physiology|volume=39|issue=3|pages=311–321|doi=10.1007/s11055-009-9128-4|issn=0097-0549|pmid=19234797}}</ref>
* Memory loss
* Anxiety
* Sleep disturbances<ref name=":0" />
* Hypertension<ref name=":0" />

As Noopept typically only displays noticeable side effects at doses above 10mg per day, and given that Noopept tends to give diminishing returns above 15mg per day, users are advised to avoid consuming more than 20mg on any given day.


==Legal status==
==Legal status==

Revision as of 11:03, 5 January 2021

N-Phenylacetyl-L-prolylglycine ethyl ester
Clinical data
Trade namesNoopept
Other namesN-Phenylacetyl-l-prolylglycine ethyl ester; GVS-111
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: Unscheduled Not FDA approved
Identifiers
  • Ethyl 1-(phenylacetyl)-l-prolylglycinate
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H22N2O4
Molar mass318.373 g·mol−1
3D model (JSmol)
  • c2ccccc2CC(=O)N1CCC[C@@H]1C(=O)NCC(=O)OCC
  • InChI=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 ☒N
  • Key:PJNSMUBMSNAEEN-AWEZNQCLSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

N-Phenylacetyl-l-prolylglycine ethyl ester is promoted as a nootropic and is a prodrug of cycloprolylglycine.[1] Other names include the brand name Noopept (Russian: Ноопепт), developmental code GVS-111; proposed INN omberacetam.[1][2][3]

Its synthesis was first reported in 1996.[1] It is orally available, and as of 2017 its metabolism and elimination half-life were not well understood, as cycloprolylglycine had not been measured in humans following administration.[1]

As of 2017 there had been many studies conducted in cells and in animal models, and there had been one clinical trial with 41 subjects, which compared Noopept and piracetam in people with traumatic brain injury.[1]

Pharmacology

Omberacetam modulates the acetylcholine system as well as the AMPA receptors.[4] This modulation essentially allows acetylcholine to accumulate at higher levels than is typical. As acetylcholine is involved in the function of memory, this could potentially account for its nootropic effects. Some research also suggests that NMDA receptors are involved in omberacetam's mechanism of action.[5][6]

Another probably mechanism of action of Noopept is neurotrophic factor expression stimulation. Animal studies show that Noopept consumption stimulates the production of both Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) in rodent brains[7]. While the effect appears to be reliable and significant across animal studies, no such studies have been carried out on humans. As such, this remains a speculative explanation for the observed nootropic effects of Noopept.

Side effects

Noopept has been known to cause side effects in a significant number of users. While these side effects are typically mild and transient at doses around 10mg per day, both the chances and severity of side effects increases as doses approach 20mg per day and upward[8]. Side effects reported in clinical data collected on humans, as well as in anecdotal reports, include:

  • Headaches
  • Irritability[9]
  • Memory loss
  • Anxiety
  • Sleep disturbances[9]
  • Hypertension[9]

As Noopept typically only displays noticeable side effects at doses above 10mg per day, and given that Noopept tends to give diminishing returns above 15mg per day, users are advised to avoid consuming more than 20mg on any given day.

Legal status

  • Russia: Noopept in Russia is a drug of medicine and is available without a prescription.[10]
  • United Kingdom: Omberacetam is illegal to produce, supply, or import under the Psychoactive Substance Act, which came into effect on May 26, 2016.[11]
  • United States: The Food and Drug Administration has issued import alerts for imports of omberacetam, considering it an analog of piracetam.[12] FDA considers such racetam-family substances Active Pharmaceutical Ingredients (APIs) that require new drug applications and adequate labelling before being imported.[13] Similarly, warnings have been issued for claims of medical and pharmacological effects of this officially non-drug substance.[14] 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.[15]

See also

External links

References

  1. ^ a b c d e "Noopept Information". Examine.com. Retrieved 6 April 2017.
  2. ^ "Proposed INN List 117" (PDF). WHO Drug Information. 31 (2): 308. 2017.
  3. ^ "GVS 111". AdisInsight. Retrieved 12 May 2018.
  4. ^ Ostrovskaia RU, Gudasheva TA, Voronina TA, Seredenin SB (September 2002). "[The original novel nootropic and neuroprotective agent noopept]". Eksperimental'naia i Klinicheskaia Farmakologiia. 65 (5): 66–72. PMID 12596521.
  5. ^ Andreeva NA, Stel'mashuk EV, Isaev NK, Ostrovskaya RU, Gudasheva TA, Viktorov IV (October 2000). "Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose deprivation, glutamate toxicity and oxidative stress". Bulletin of Experimental Biology and Medicine. 130 (10): 969–72. doi:10.1007/BF02682041. PMID 11177296. S2CID 20572688.
  6. ^ Kovalev GI, Vorob'ev VV, Akhmetova ER (August 1999). "NMDA component in the effects of piracetam and new nootropic peptide GVS-111 on the neocortical and hippocampal EEG in conscious rats". Bulletin of Experimental Biology and Medicine. 128 (2): 822–5. doi:10.1007/BF02433825. S2CID 20090927.
  7. ^ Ostrovskaya, R. U.; Gudasheva, T. A.; Zaplina, A. P.; Vahitova, Ju V.; Salimgareeva, M. H.; Jamidanov, R. S.; Seredenin, S. B. (2008-09). "Noopept stimulates the expression of NGF and BDNF in rat hippocampus". Bulletin of Experimental Biology and Medicine. 146 (3): 334–337. doi:10.1007/s10517-008-0297-x. ISSN 0007-4888. PMID 19240853. {{cite journal}}: Check date values in: |date= (help)
  8. ^ Tardner, Paul. "Finding the optimal dosage for nootropic agent Noopept: An analysis of available literature" (PDF). International Journal of Environmental Science and Technology.
  9. ^ a b c Neznamov, G. G.; Teleshova, E. S. (2009-03). "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. doi:10.1007/s11055-009-9128-4. ISSN 0097-0549. PMID 19234797. {{cite journal}}: Check date values in: |date= (help)
  10. ^ "Государственный реестр лекарственных средств".
  11. ^ "Psychoactive Substances Act 2016". Legislation.gov.uk.
  12. ^ Cohen, Pieter A.; Zakharevich, Igor; Gerona, Roy (1 March 2020). "Presence of Piracetam in Cognitive Enhancement Dietary Supplements". JAMA Internal Medicine. 180 (3): 458–459. doi:10.1001/jamainternmed.2019.5507. PMC 6902196. PMID 31764936.
  13. ^ "Import alert 66-66".
  14. ^ "FDA Warning letter: Peak Nootropics LLC aka Advanced Nootropics".
  15. ^ Cohen, Pieter A.; Avula, Bharathi; Wang, Yan Hong; Zakharevich, Igor; Khan, Ikhlas (23 September 2020). "Five unapproved drugs found in cognitive enhancement supplements". Neurology: Clinical Practice: 10.1212/CPJ.0000000000000960. doi:10.1212/CPJ.0000000000000960.
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