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(S)-CPW 399 is a potent and selective agonist of AMPA receptor with Ki value of 747 nM [1].

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor) is an ionotropic transmembrane receptor for glutamate and mediates fast synaptic transmission in the central nervous system. AMPA receptors are oligomeric assemblies of four protein subunits, GluR1-4.

(S)-CPW 399 is a potent and selective AMPA receptor agonist. (S)-CPW 399 exhibited affinity with Ki values of 109, 218, 2137 and 1756 nM for GluR1, GluR2, GluR3 and GluR4 receptors, respectively [1]. In mouse cerebellar granule cells, (S)-CPW 399 induced neuronal cell death in a concentration- and time-dependent way with EC50 value of 70 μM and increased intracellular free-calcium levels ([Ca2+]i ) in a concentration-dependent way with EC50 value of 5 μM [2]. In rat cerebellar granule cells, CPW-399 increased the expression of GABAA receptor δ subunit, which relied on NMDA receptor activation [3]. In Sf9 cells expressing iGluR5, (S)-CPW 399 exhibited affinity for iGluR5 with Ki value of 44 nM. In Xenopus læVis Oocytes, (S)-CPW 399 exhibited agonist activity with EC50 values of 24.9, 13.9, 224 and 34.3 μM for iGluR1, iGluR2, iGluR3 and iGluR4 receptors, respectively [4].

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