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Methylphenylpiracetam
Names
	IUPAC name 2-(5-Methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide
Identifiers
CAS Number	1301211-78-8 [ChemSpider];
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL2391147;
ChemSpider	30831670;
PubChem CID	52912210;
CompTox Dashboard (EPA)	DTXSID601031901 ;
	InChI InChI=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 Key: ZTGRWYMPQCQTHD-ONGXEEELSA-N;
	SMILES C[C@H]1[C@H](CC(=O)N1CC(=O)N)C2=CC=CC=C2;
Properties
Chemical formula	C13H16N2O2
Molar mass	232.283 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Methylphenylpiracetam is a derivative of piracetam and a positive allosteric modulator of the sigma-1 receptor.^[1]^[2]^[3] It differs from phenylpiracetam by having a methyl group.^[2]

E1R is the (4R,5S) stereoisomer of methylphenylpiracetam that has been shown to have the greatest effect on the modulation of the sigma-1 receptor.^[2]

Enantiomers

The two R-configuration enantiomers, i.e. (4R,5S) and (4R,5R), of methylphenylpiracetam are more active positive allosteric modulators of the sigma-1 receptor than the two S-configuration enantiomers, i.e. (4S,5R) and (4S,5S).^[1]^[3]

Enantiomer	σ₁R PAM effect %^[3]
erythro-(4R,5S)	222 ± 37
threo-(4R,5R)	191 ± 23
erythro-(4S,5R)	141 ± 40
threo-(4S,5S)	147 ± 31

Effects

E1R enhances cognition and has efficacy against cholinergic dysfunction in mice without affecting locomotor activity.^[2] Pretreatment with E1R enhanced the σ₁R agonist PRE-084's stimulating effect and facilitated passive avoidance retention.^[2] It alleviated scopolamine-induced cognitive impairment.^[2] The cognition enhancing activity of E1R is higher than that of (R)-phenylpiracetam.^[4]

Because E1R had no effect on locomotor activity, it was found to be free of potential motor side effects.^[2]

Legality

Australia

Methylphenylpiracetam is a schedule 4 substance in Australia under the Poisons Standard (February 2020).^[5] 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."^[5]

References

^ ^a ^b Vavers E, Zvejniece L, Veinberg G, Svalbe B, Domracheva I, Vilskersts R, Dambrova M (2015). "Novel positive allosteric modulators of sigma-1 receptor". SpringerPlus. 4 (Suppl 1): P51. doi:10.1186/2193-1801-4-S1-P51. PMC 4797911. The R-configuration enantiomers of methylphenylpiracetam are more active positive allosteric modulators of Sigma-1 receptor than S-configuration enantiomers.
^ ^a ^b ^c ^d ^e ^f ^g Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M (2014). "The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors". British Journal of Pharmacology. 171 (3): 761–71. doi:10.1111/bph.12506. PMC 3969087. PMID 24490863.
^ ^a ^b ^c Veinberg, G; Vorona, M; Zvejniece, L; Vilskersts, R; Vavers, E; Liepinsh, E; Kazoka, H; Belyakov, S; Mishnev, A; Kuznecovs, J; Vikainis, S; Orlova, N; Lebedev, A; Ponomaryov, Y; Dambrova, M (2013). "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". Bioorganic & Medicinal Chemistry. 21 (10): 2764–71. doi:10.1016/j.bmc.2013.03.016. PMID 23582449.
^ Veinberg G, Vavers E, Orlova N, Kuznecovs J, Domracheva I, Vorona M, Zvejniece L, Dambrova M (2015). "Stereochemistry of phenylpiracetam and its methyl derivative: improvement of the pharmacological profile". Chemistry of Heterocyclic Compounds. 51 (7): 601–606. doi:10.1007/s10593-015-1747-9. S2CID 93449199. 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.
^ ^a ^b Poisons Standard February 2020. comlaw.gov.au