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.
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 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].
[1]. M?ller A, et al. Pharmacological profile and anti-ischemic properties of the Ca(2+)-channel blocker NS-638. Neurol Res. 1995 Oct;17(5):353-60.