{{Chembox | ImageFile = E1R.svg | ImageClass = skin-invert-image | ImageSize = 150px | ImageAlt = | IUPACName = 2-(5-Methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide | OtherNames = | Section1 = {{Chembox Identifiers | CASNo = 1301211-78-8 | CASNo_Ref = {{Cascite|changed|ChemSpider}} | ChEMBL = 2391147 | PubChem = 52912210 | ChemSpiderID = 30831670 | SMILES = C[C@H]1[C@H](CC(=O)N1CC(=O)N)C2=CC=CC=C2 | StdInChI = 1S/C13H16N2O2/c1-9-11(10-5-3-2-4-6-10)7-13(17)15(9)8-12(14)16/h2-6,9,11H,7-8H2,1H3,(H2,14,16)/t9-,11-/m0/s1 | StdInChIKey = ZTGRWYMPQCQTHD-ONGXEEELSA-N }} | Section2 = {{Chembox Properties | C=13|H=16|N=2|O=2 | MolarMass = | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = }} | Section3 = {{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }}
'''Methylphenylpiracetam''' is a derivative of piracetam and a positive allosteric modulator of the sigma-1 receptor.<ref name="4-S1-P51">{{cite journal | year = 2015 | title = Novel positive allosteric modulators of sigma-1 receptor | vauthors = Vavers E, Zvejniece L, Veinberg G, Svalbe B, Domracheva I, Vilskersts R, Dambrova M | doi = 10.1186/2193-1801-4-S1-P51 | quote = The R-configuration enantiomers of methylphenylpiracetam are more active positive allosteric modulators of Sigma-1 receptor than S-configuration enantiomers. | volume=4 | issue = Suppl 1 | journal=SpringerPlus | pages=P51| pmc = 4797911 | doi-access = free }}</ref><ref name="pmid24490863">{{Cite journal | pmid = 24490863 | pmc = 3969087 | year = 2014 | last1 = Zvejniece | first1 = L | title = The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors | journal = British Journal of Pharmacology | volume = 171 | issue = 3 | pages = 761–71 | last2 = Vavers | first2 = E | last3 = Svalbe | first3 = B | last4 = Vilskersts | first4 = R | last5 = Domracheva | first5 = I | last6 = Vorona | first6 = M | last7 = Veinberg | first7 = G | last8 = Misane | first8 = I | last9 = Stonans | first9 = I | last10 = Kalvinsh | first10 = I | last11 = Dambrova | first11 = M | doi = 10.1111/bph.12506 }}</ref><ref name="pmid23582449">{{Cite journal | pmid = 23582449 | year = 2013 | last1 = Veinberg | first1 = G | title = Synthesis and biological evaluation of 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide stereoisomers as novel positive allosteric modulators of sigma-1 receptor | journal = Bioorganic & Medicinal Chemistry | volume = 21 | issue = 10 | pages = 2764–71 | last2 = Vorona | first2 = M | last3 = Zvejniece | first3 = L | last4 = Vilskersts | first4 = R | last5 = Vavers | first5 = E | last6 = Liepinsh | first6 = E | last7 = Kazoka | first7 = H | last8 = Belyakov | first8 = S | last9 = Mishnev | first9 = A | last10 = Kuznecovs | first10 = J | last11 = Vikainis | first11 = S | last12 = Orlova | first12 = N | last13 = Lebedev | first13 = A | last14 = Ponomaryov | first14 = Y | last15 = Dambrova | first15 = M | doi = 10.1016/j.bmc.2013.03.016 | url = https://docs.google.com/file/d/0B_01lUL0-VEweUJjcGZZTTIxMTA | url-access = subscription }}</ref> It differs from phenylpiracetam by having a methyl group.<ref name="pmid24490863"/> <!--quote: E1R is a close structural analogue of these two compounds, which differ in structure [from E1R] by only one methyl group-->
'''E1R''' is the (4''R'',5''S'') stereoisomer of methylphenylpiracetam that has been shown to have the greatest effect on the modulation of the sigma-1 receptor.<ref name="pmid24490863"/>
==Enantiomers== The two R-configuration enantiomers, i.e. (4''R'',5''S'') and (4''R'',5''R''), of methylphenylpiracetam are more active positive allosteric modulators of the sigma-1 receptor than the two S-configuration enantiomers, i.e. (4''S'',5''R'') and (4''S'',5''S'').<ref name="4-S1-P51"/><ref name="pmid23582449"/>
{| class="wikitable sortable" |- ! Enantiomer !! σ<sub>1</sub>R PAM effect %<ref name="pmid23582449"/> |- | ''erythro''-(4''R'',5''S'') || 222 ± 37 |- | ''threo''-(4''R'',5''R'') || 191 ± 23 |- | ''erythro''-(4''S'',5''R'') || 141 ± 40 |- | ''threo''-(4''S'',5''S'') || 147 ± 31 |}
==Effects== E1R enhances cognition and has efficacy against cholinergic dysfunction in mice without affecting locomotor activity.<ref name="pmid24490863"/> Pretreatment with E1R enhanced the σ<sub>1</sub>R agonist PRE-084's stimulating effect and facilitated passive avoidance retention.<ref name="pmid24490863"/> It alleviated scopolamine-induced cognitive impairment.<ref name="pmid24490863"/> The cognition enhancing activity of E1R is higher than that of (''R'')-phenylpiracetam.<ref name="veinberg2015">{{Cite journal | year = 2015 | volume = 51 | issue = 7 | pages = 601–606 | vauthors = Veinberg G, Vavers E, Orlova N, Kuznecovs J, Domracheva I, Vorona M, Zvejniece L, Dambrova M | title = Stereochemistry of phenylpiracetam and its methyl derivative: improvement of the pharmacological profile | journal = Chemistry of Heterocyclic Compounds | quote = In conclusion, the obtained data demonstrated that E1R is the most active memory enhancing enantiomer of the 5-methyl-substituted phenylpiracetam homolog, and its cognition enhancing activity is higher than that of (R)-phenylpiracetam. | doi=10.1007/s10593-015-1747-9| s2cid = 93449199 }}<!--This is a review article.--></ref>
Because E1R had no effect on locomotor activity, it was found to be free of potential motor side effects.<ref name="pmid24490863"/>
== Legality == === Australia === Methylphenylpiracetam is a schedule 4 substance in Australia under the Poisons Standard (February 2020).<ref name="Poisons Stanrard">[https://www.legislation.gov.au/Details/F2020C00148 Poisons Standard February 2020]. comlaw.gov.au</ref> A schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."<ref name="Poisons Stanrard" />
==See also== * Diastereomer * List of Russian drugs
== References == {{reflist | 30em}}
==External links== * [https://web.archive.org/web/20181031200646/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969087/bin/bph0171-0761-sd1.docx Screening profile of 10 μM E1R in vitro binding assays] (docx) <!-- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969087/ -->
==Further reading== * {{US patent reference | number = 8791273 | y = 2014 | m = 07 | d = 29 | inventor = Kalvins, et al. | title = [http://patft.uspto.gov/netacgi/nph-Parser?patentnumber=8791273 4R,5S-enantiomer of 2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide with nootropic activity] }}<!--Issue date unclear.-->
{{Sigmaergics}} {{Racetams}}
Category:Racetams Category:Receptor modulators