NS-638

NS-638 is a small nonpeptide molecule with Ca²⁺-channel blocking properties. K⁺-stimulated intracellular Ca²⁺-elevation is blocked with an IC₅₀ value of 3.4 μM. IC50 & Target: IC50: 3.4 μM (K⁺-stimulated intracellular Ca²⁺-elevation) ^[1] In Vitro: NS-638 dose dependently inhibits K⁺-stimulated [45 Ca²⁺]-uptake in chick cortical synaptosomes and 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)- stimulated [³H]GABA-release from cultured cortical neurons with IC₅₀ values of 2.3 and 4.3 μM, respectively. K⁺-stimulated intracellular Ca²⁺-elevation in cultured cerebellar granule cells is equipotently blocked with an IC₅₀ value of 3.4 μM. At this concentration no effect on Ca²⁺-induced contractions in K⁺-depolarized guinea pig taenia coli is observed. NS-638 reversibly blocks N- and L-type Ca²⁺-channels in cultured chick dorsal root ganglion cells in the concentration range of 1-30 μM^[1]. In Vivo: In the mouse middle cerebral artery occlusion model, NS-638 administered i.p. (50 mg kg-1) at 1 h and 6 h post-ischemia, and once a day for the next two days, results in a 48% reduction in total infarct volume. It does not show protection against ischemic neuronal damage in the gerbil model of bilateral carotid artery occlusion^[1].