| Revision as of 05:42, 19 April 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (no changed fields - added verified revid - updated 'UNII_Ref', 'ChemSpiderID_Ref', 'StdInChI_Ref', 'StdInChIKey_Ref', 'ChEMBL_Ref', 'KEGG_Ref') per Chem/Drugbox validation (← Previous edit |
Latest revision as of 03:25, 22 December 2024 edit undoRcfische2 (talk | contribs)106 edits WP SYNTH, articles might support “no safe dose.” But don’t think this is the place to state it. |
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{{short description|Prodrug}} |
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{{drugbox |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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| verifiedrevid = 406111365 |
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{{more medical citations needed|date=January 2021}} |
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| IUPAC_name = N-phenylacetyl-L-prolylglycine ethyl ester |
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{{DISPLAYTITLE:''N''-Phenylacetyl-<small>L</small>-prolylglycine ethyl ester}} |
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| image = Noopept_structure.png |
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{{Infobox drug |
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| width = 220 |
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| CAS_number = 157115-85-0 |
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| ATC_prefix = |
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| Watchedfields = changed |
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| ATC_suffix = |
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| verifiedrevid = 424810394 |
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| drug_name = ''N''-Phenylacetyl-<small>L</small>-prolylglycine ethyl ester |
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| PubChem = 180496 |
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| IUPAC_name = Ethyl 1-(phenylacetyl)-{{sm|l}}-prolylglycinate |
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| DrugBank = |
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| image = Noopept.svg |
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| C=17|H=22|N=2|O=4 |
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| width = 220 |
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| molecular_weight = 318.367 g/mol |
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| smiles = c2ccccc2CC(=O)N1CCCC1C(=O)NCC(=O)OCC |
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| image2 = Noopept.png |
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| bioavailability = |
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<!--Clinical data-->| tradename = Noopept |
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| protein_bound = |
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| pregnancy_AU = <!-- A, B1, B2, B3, C, D, X --> |
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| metabolism = |
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| pregnancy_US = <!-- A, B, C, D, X --> |
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| elimination_half-life = |
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| excretion = |
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| legal_AU = S4 |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| legal_UK = <!-- GSL, P, POM, CD, Class A, B, C --> |
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| legal_US = Unapproved "New Drug" (as defined by 21 U.S. Code § 321(p)(1)). Use in ]s, ], or ] is unlawful; otherwise uncontrolled. |
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| pregnancy_category= |
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| legal_US_comment = |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_status = <!--Identifiers--> |
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| CAS_number = 157115-85-0 |
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| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> |
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| CAS_number_Ref = {{cascite|correct|CAS}} |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = legal |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 4QBJ98683M |
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| routes_of_administration = |
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| PubChem = 180496 |
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| synonyms = omberacetam; GVS-111; DVD-111; SGS-111; benzylcarbonyl-Pro-Gly-OEt |
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<!--Chemical data-->| C = 17 |
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| H = 22 |
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| N = 2 |
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| O = 4 |
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| SMILES = c2ccccc2CC(=O)N1CCC1C(=O)NCC(=O)OCC |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 157065 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| 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 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = PJNSMUBMSNAEEN-AWEZNQCLSA-N |
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}} |
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'''''N''-Phenylacetyl-{{sm|l}}-prolylglycine ethyl ester''' is promoted as a ] and is a ] of ].{{efn|Referring to the cyclic dipeptide better known as cyclo(prolylglycyl), i.e. (S)-hexahydropyrrolopyrazine-1,4-dione<!--Q27095302-->.<ref>{{cite web | title = Omberacetam | url = https://drugs.ncats.io/drug/4QBJ98683M | work = Inxight | publisher = National Center for Advancing Translational Sciences (NCATS) | id = 4QBJ98683M }}</ref> Not to be confused with a ] moiety.}}<ref name=Examine>{{cite web|title=Noopept Information|url=http://examine.com/supplements/Noopept/|publisher=]|access-date=6 April 2017}}</ref> Other names include the brand name '''Noopept''' ({{langx|ru|link=no|Ноопепт}}), developmental code '''GVS-111''', and proposed ] '''omberacetam'''.<ref name=Examine/><ref>{{cite journal|title=Proposed INN List 117|journal=WHO Drug Information|date=2017|volume=31|issue=2|page=308|url=https://www.who.int/publications/m/item/inn-pl-117}}</ref><ref>{{cite web|title= Omberacetam | quote = Alternative Names: DVD-111; GVS 111; Noopept |url=https://adisinsight.springer.com/drugs/800006775 | work = AdisInsight | publisher = Springer Nature Switzerland AG |access-date=12 May 2018|language=en}}</ref> |
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'''Noopept''' ({{lang-ru|Ноопепт}}; '''GVS-111''', '''N-phenylacetyl-L-prolylglycine ethyl ester''') is a medication promoted and prescribed in ] and ] as a ] remedy. It is derived from the ] family of drugs and shares similar mechanisms of action,<ref>Solntseva EI, Bukanova JV, Ostrovskaya RU, Gudasheva TA, Voronina TA, Skrebitsky VG. The effects of piracetam and its novel peptide analogue GVS-111 on neuronal voltage-gated calcium and potassium channels. ''General Pharmacology''. 1997 Jul;29(1):85-9. PMID 9195198</ref><ref>Gudasheva TA, Boyko SS, Ostrovskaya RU, Voronina TA, Akparov VK, Trofimov SS, Rozantsev GG, Skoldinov AP, Zherdev VP, Seredenin SB. The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine. ''European Journal of Drug Metabolism and Pharmacokinetics''. 1997 Jul-Sep;22(3):245-52. PMID 9358206</ref> but is up to 1000 times more potent than the prototypical racetam drug, ].<ref name="pmid12596521">{{cite journal |author=Ostrovskaia RU, Gudasheva TA, Voronina TA, Seredenin SB |title= |language=Russian |journal=] |volume=65 |issue=5 |pages=66–72 |year=2002 |pmid=12596521 |doi= |url=}}</ref> Animal studies have shown noopept to be ] and enhance memory in various different tests.<ref>Ostrovskaya RU, Romanova GA, Barskov IV, Shanina EV, Gudasheva TA, Victorov IV, Voronina TA, Seredenin SB. Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model. ''Behavioural Pharmacology''. 1999 Sep;10(5):549-53. PMID 10780261</ref><ref>Pelsman A, Hoyo-Vadillo C, Gudasheva TA, Seredenin SB, Ostrovskaya RU, Busciglio J. GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons. ''International Journal of Developmental Neuroscience''. 2003 May;21(3):117-24. PMID 12711349</ref><ref>Ostrovskaya RU, Gruden MA, Bobkova NA, Sewell RD, Gudasheva TA, Samokhin AN, Seredinin SB, Noppe W, Sherstnev VV, Morozova-Roche LA. The nootropic and neuroprotective proline-containing dipeptide noopept restores spatial memory and increases immunoreactivity to amyloid in an Alzheimer's disease model. ''Journal of Psychopharmacology''. 2007 Aug;21(6):611-9. PMID 17092975</ref><ref>Ostrovskaya RU, Gudasheva TA, Zaplina AP, Vahitova JV, Salimgareeva MH, Jamidanov RS, Seredenin SB. Noopept stimulates the expression of NGF and BDNF in rat hippocampus. ''Bulletin of Experimental Biology and Medicine''. 2008 Sep;146(3):334-7.PMID: 19240853</ref> Unusually for a peptide-derived compound, noopept displays both high ] and good ] penetration,<ref>Boiko SS, Ostrovskaya RU, Zherdev VP, Korotkov SA, Gudasheva TA, Voronina TA, Seredenin SB. Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration. ''Bulletin of Experimental Biology and Medicine''. 2000 Apr;129(4):359-61. PMID 10977920</ref><ref>Ostrovskaya RU, Mirsoev TK, Romanova GA, Gudasheva TA, Kravchenko EV, Trofimov CC, Voronina TA, Seredenin SB. Proline-containing dipeptide GVS-111 retains nootropic activity after oral administration. ''Bulletin of Experimental Biology and Medicine''. 2001 Oct;132(4):959-62. PMID 11782792</ref> and human studies have shown promising results, with potential application in the treatment of ].<ref>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 Behavioural Physiology''. 2009 Mar;39(3):311-21. PMID 19234797</ref> |
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Its synthesis was first reported in 1996.<ref name=Examine/> It is orally available. As of 2017, its metabolism and elimination half-life in humans were not well understood.<ref name=Examine/> |
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==References== |
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{{reflist}} |
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It has been evaluated for ] effects in treating brain injuries and stroke.<ref name="Ostrovskaia_2002">{{cite journal | vauthors = Ostrovskaia RU, Gudasheva TA, Voronina TA, Seredenin SB | title = | language = Russian | journal = Eksperimental'naia i Klinicheskaia Farmakologiia | volume = 65 | issue = 5 | pages = 66–72 | date = 2002 | pmid = 12596521 | doi = | trans-journal = Experimental and Clinical Pharmacology | trans-title = The original novel nootropic and neuroprotective agent noopept }}</ref> |
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==Pharmacology== |
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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 ] of excess calcium and glutamate, and to improve the blood ]".<ref name="Ostrovskaia_2002" /> Studies in rats suggest, Noopept is a prodrug of the endogenous dipeptide ].<ref>{{cite journal | vauthors = Gudasheva TA, Boyko SS, Ostrovskaya RU, Voronina TA, Akparov VK, Trofimov SS, Rozantsev GG, Skoldinov AP, Zherdev VP, Seredenin SB | title = The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine | journal = European Journal of Drug Metabolism and Pharmacokinetics | volume = 22 | issue = 3 | pages = 245–252 | date = 1997 | pmid = 9358206 | doi = 10.1007/BF03189814 }}</ref> ] is a modulator of ] receptors and exerts neuroprotective effects dependent upon ]- and ]-Receptor activation.<ref>{{cite journal | vauthors = Gudasheva TA, Koliasnikova KN, Alyaeva AG, Nikolaev SV, Antipova TA, Seredenin SB | title = Neuroprotective Effect of the Neuropeptide Cycloprolylglycine Depends on AMPA- and TrkB-Receptor Activation | journal = Doklady. Biochemistry and Biophysics | volume = 507 | issue = 1 | pages = 264–267 | date = December 2022 | pmid = 36786983 | doi = 10.1134/S1607672922060047 }}</ref> In cell culture, cycloprolylglycine increases ] (BDNF).<ref>{{cite journal | vauthors = Gudasheva TA, Koliasnikova KN, Antipova TA, Seredenin SB | title = Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells | journal = Doklady. Biochemistry and Biophysics | volume = 469 | issue = 1 | pages = 273–276 | date = July 2016 | pmid = 27599510 | doi = 10.1134/S1607672916040104 | s2cid = 254426990 }}</ref> |
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Some studies suggest that the pharmacological properties of Noopept are derived from its action as an activator of ] (HIF-1).<ref>{{cite journal | vauthors = Zainullina LF, Ivanova TV, Sadovnikov SV, Vakhitova YV, Seredenin SB | title = Cognitive Enhancer Noopept Activates Transcription Factor HIF-1 | journal = Doklady. Biochemistry and Biophysics | volume = 494 | issue = 1 | pages = 256–260 | date = September 2020 | pmid = 33119829 | doi = 10.1134/S1607672920050129 | s2cid = 226207175 }}</ref><ref name=":0">{{cite journal | vauthors = Vakhitova YV, Sadovnikov SV, Borisevich SS, Ostrovskaya RU, A Gudasheva T, Seredenin SB | title = Molecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept | journal = Acta Naturae | volume = 8 | issue = 1 | pages = 82–89 | year = 2016 | pmid = 27099787 | pmc = 4837574 | doi = 10.32607/20758251-2016-8-1-82-89 }}</ref> |
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== Dosage == |
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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.{{ums|date=December 2021}}<ref>{{Cite journal| vauthors = Tardner P |date=2020|title=Finding the optimal dosage fornootropic agent Noopept: An analysis of available literature|url=http://ijest.org/Noopept_Dosage_PTardner1120.pdf|journal=International Journal of Environmental Science and Technology}}</ref> 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.<ref>{{cite journal | vauthors = Neznamov GG, Teleshova ES | 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 | journal = Neuroscience and Behavioral Physiology | volume = 39 | issue = 3 | pages = 311–321 | date = March 2009 | pmid = 19234797 | doi = 10.1007/s11055-009-9128-4 | s2cid = 3348153 }}</ref> |
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==Legal status== |
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*'''Hungary:''' As of 25 August 2020, Noopept is added to the controlled psychoactive substances list, prohibiting production, sale, import, storage and use.<ref>{{cite journal | vauthors = Miklós K | date = 25 August 2020 | volume = 194 | pages = 6135–6142 (6139) | title = Az új pszichoaktív anyaggá minősített anyagokról vagy vegyületcsoportokról szóló 55/2014. (XII. 30.) EMMI rendelet módosításáról | trans-title = About substances classified as new psychoactive substances or 55/2014 on groups of compounds (XII. 30.) amending the EMMI Decree | url = https://magyarkozlony.hu/hivatalos-lapok/fsmDhb9y0CRKX2SkxRDw5f37b222dc2d1/dokumentumok/bc9ef7aef40a107a518ab17e1ac35adf2735e291/letoltes | journal = Magyarország Hivatalos Lapja | trans-journal = Official Journal of Hungary | language = Hungarian | access-date = 28 April 2021 }}</ref> |
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*'''Russia:''' Noopept in Russia is a drug of medicine and is available without a prescription.<ref>{{cite web | title = Ноопепт | trans-title = Noopept | work = Государственный реестр лекарственных средств | trans-work = State Register of Medicines | language = Russian | url = http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=6e1f901d-6924-4721-87d5-c82880be8286&t= }}</ref> |
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*'''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.<ref>{{cite web | title = Psychoactive Substances Act 2016 | work = Legislation.gov.uk | url = http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted }}</ref> However, sale and supply for human consumption are prohibited. |
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*'''United States:''' The ] has issued import alerts for imports of omberacetam, considering it an analog of ].<ref>{{cite journal | vauthors = Cohen PA, Zakharevich I, Gerona R | title = Presence of Piracetam in Cognitive Enhancement Dietary Supplements | journal = JAMA Internal Medicine | volume = 180 | issue = 3 | pages = 458–459 | date = March 2020 | pmid = 31764936 | pmc = 6902196 | doi = 10.1001/jamainternmed.2019.5507 }}</ref> FDA considers such racetam-family substances Active Pharmaceutical Ingredients (APIs) that require new drug applications and adequate labelling before being imported.<ref>{{cite web | url = https://www.accessdata.fda.gov/cms_ia/importalert_202.html | title = Import alert 66-66 | publisher = U.S. Food and Drug Administration | date = 7 September 2021 }}</ref> Similarly, warnings have been issued for claims of medical and pharmacological effects.<ref>{{cite web | url = https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/peak-nootropics-llc-aka-advanced-nootropics-557887-02052019 | work = FDA Warning letter | date = 5 February 2019 | title = Peak Nootropics LLC aka Advanced Nootropics | publisher = U.S. Food and Drug Administration | vauthors = Correll Jr WA }}</ref> 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.<ref>{{cite journal | vauthors = Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I | title = Five Unapproved Drugs Found in Cognitive Enhancement Supplements | journal = Neurology. Clinical Practice | volume = 11 | issue = 3 | pages = e303–e307 | date = June 2021 | pmid = 34484905 | pmc = 8382366 | doi = 10.1212/CPJ.0000000000000960 }}</ref> |
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== See also == |
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* ] |
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* ] |
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== Notes == |
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{{Notelist}} |
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== References == |
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{{Reflist}} |
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{{Antihyperkinetics}} |
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{{Antihyperkinetics}} |
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{{Racetams}} |
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{{Racetams}} |
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{{DEFAULTSORT:Phenylacetyl-L-prolylglycine ethyl ester, N-}} |
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