SX-3228 is a selective agonist of benzodiazepine1 (BZ1) receptor(IC50 of 17 nM).

BZ1 receptor:17 nM

SX-3228 is a selective ligand for the BZ1 receptor, binding preferentially with an IC50 of 17 nM. It exhibits very weak affinity for the BZ2 receptor (spinal cord: IC50=127 nM) and negligible affinity for the peripheral type BZ receptor (kidney: IC50>10000 nM). SX-3228 does not bind to dopamine (D1, D2), serotonin (5-HT1, 5-HT2, 5-HT3), noradrenaline (α1, α2, β), GABA, or acetylcholine (muscarinic) subtypes.

Administering SX-3228 at doses ranging from 0.5 to 2.5 mg/kg to rats during their active (light) phase significantly diminishes rapid-eye-movement sleep (REMS) (P<0.05), particularly in the third hour of observation. Conversely, introducing SX-3228 in the same dosage range at the onset of the inactive (dark) phase profoundly alters sleep architecture: it markedly reduces wakefulness (W) and enhances slow-wave sleep (SWS) throughout a 6-hour examination period in a dose-dependent manner (P<0.05-0.01). Notably, these significant effects in the final hour are exclusively observed at the highest administered dose of 2.5 mg/kg (P<0.01).