(R)-AS-1

(R)-AS-1 is a positive allosteric modulator of excitatory amino acid transporter 2 (EAAT2; EC₅₀ = 11 nM in a glutamate uptake assay).¹ It is selective for EAAT2 over EAAT1, EAAT3, and a panel of 30 other ion channels, transporters, receptors, and enzymes. (R)-AS-1 (60 and 90 mg/kg) increases spontaneous locomotor activity in mice. It has anticonvulsant activity in mouse models of seizures induced by maximal electroshock (MES), pentylenetetrazole (PTZ), or electrical stimuli of 32 or 44 mA (ED₅₀s = 66.3, 36.3, 15.6, and 41.6 mg/kg, respectively).

References:
[1]. Abram, M., Jakubiec, M., Reeb, K., et al.Discovery of (R)-N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a novel orally bioavailable EAAT2 modulator with drug-like properties and potent antiseizure activity in vivoJ. Med. Chem.65(17)11703-11725(2022).