Chemistry:Methylphenylpiracetam
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]
See also
- Diastereomer
- List of Russian drugs
References
- ↑ 1.0 1.1 "Novel positive allosteric modulators of sigma-1 receptor". SpringerPlus 4 (Suppl 1): P51. 2015. 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.".
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I et al. (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. PMID 24490863.
- ↑ 3.0 3.1 3.2 Veinberg, G; Vorona, M; Zvejniece, L; Vilskersts, R; Vavers, E; Liepinsh, E; Kazoka, H; Belyakov, S et al. (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. https://docs.google.com/file/d/0B_01lUL0-VEweUJjcGZZTTIxMTA.
- ↑ "Stereochemistry of phenylpiracetam and its methyl derivative: improvement of the pharmacological profile". Chemistry of Heterocyclic Compounds 51 (7): 601–606. 2015. 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.".
- ↑ 5.0 5.1 Poisons Standard February 2020. comlaw.gov.au
External links
Further reading
- US patent 8791273, Kalvins, et al., "4R,5S-enantiomer of 2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide with nootropic activity", issued 2014-07-29
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