Methylphenylpiracetam

Methylphenylpiracetam
Names
IUPAC name
2-(5-Methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide
Identifiers
3D model (JSmol)
Properties
C13H16N2O2
Molar mass 232.28 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.[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]

See also

References

  1. 1 2 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: P51. doi:10.1186/2193-1801-4-S1-P51. The R-configuration enantiomers of methylphenylpiracetam are more active positive allosteric modulators of Sigma-1 receptor than S-configuration enantiomers.
  2. 1 2 3 4 5 6 7 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. PMC 3969087 Freely accessible. PMID 24490863. doi:10.1111/bph.12506.
  3. 1 2 3 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. PMID 23582449. doi:10.1016/j.bmc.2013.03.016.
  4. ↑ 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. 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.

Further reading


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