SEA0400

SEA0400 is a novel and selective inhibitor of the Na⁺-Ca²⁺ exchanger (NCX), inhibiting Na⁺-dependent Ca²⁺ uptake in cultured neurons, astrocytes, and microglia with IC₅₀s of from 5 to 33 nM. IC50 & Target: IC50: 5-33 nM (NCX) In Vitro: SEA0400 inhibits Na⁺-dependent ⁴⁵Ca²⁺ uptake in cultured neurons, astrocytes, and microglia. IC₅₀ values of SEA0400 are 33 nM (neurons), 5.0 nM (astrocytes), and 8.3 nM (microglia)^[1]. SEA0400 prevents sodium nitroprusside (SNP) to increase ERK and p38 MAPK phosphorylation, and production of reactive oxygen species (ROS) in an extracellular Ca²⁺-dependent manner^[2]. In Vivo: SEA0400 (3 mg/kg + 3 mg/kg/h for 2 h, i.v.) attenuates the infarct volume in the cerebral cortex and striatum, does not affect the mean the regional cortical blood flow in anesthetized rats^[1]. SEA0400 protects against the dopaminergic neurotoxicity (determined by dopamine levels in the midbrain and striatum, tyrosine hydroxylase immunoreactivity in the substantia nigra and striatum, striatal dopamine release, and motor deficits) in MPTP-treated C57BL/6J mice^[3].