3D model (JSmol)
|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).
Methylphenylpiracetam is a derivative of piracetam and a positive allosteric modulator of the sigma-1 receptor. It differs from phenylpiracetam by having a methyl group.
E1R is the (4R,5S) stereoisomer of methylphenylpiracetam.
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).
|Enantiomer||σ1R PAM effect %|
|erythro-(4R,5S)||222 ± 37|
|threo-(4R,5R)||191 ± 23|
|erythro-(4S,5R)||141 ± 40|
|threo-(4S,5S)||147 ± 31|
E1R enhances cognition and has efficacy against cholinergic dysfunction in mice without affecting locomotor activity. Pretreatment with E1R enhanced the σ1R agonist PRE-084's stimulating effect and facilitated passive avoidance retention. It alleviated scopolamine-induced cognitive impairment. The cognition enhancing activity of E1R is higher than that of (R)-phenylpiracetam.
Because E1R had no effect on locomotor activity, it was found to be free of potential motor side effects.
Methylphenylpiracetam is a schedule 4 substance in Australia under the Poisons Standard (February 2020). 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."
The R-configuration enantiomers of methylphenylpiracetam are more active positive allosteric modulators of Sigma-1 receptor than S-configuration enantiomers.
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.