NS 8593 is an inhibitory gating modifier of small conductance calcium-activated potassium (SK) channels (Kds = 0.42, 0.6, and 0.73 μM for SK1, SK2, and SK3, respectively, in the presence of calcium) that decreases the calcium sensitivity of SK channels.[1] It is selective for SK channels over intermediate (IK) and large conductance (BK) potassium channels at 10 μM. NS 8593 induces relaxation of potassium- or acetylcholine chloride-precontracted isolated tracheal rings from wild-type mice (IC50s = 8.9 and 39.8 μM, respectively) or from mice in an ovalbumin-induced model of allergic asthma (IC50s = 16.4 and 32.2 μM, respectively).[2] It inhibits aerosolized acetylcholine chloride-induced increases in respiratory system resistance in mice when administered as an aerosol at a dose of 500 μM. NS 8593 (5 mg/kg) decreases the duration of burst-pacing-induced atrial fibrillation in normotensive and spontaneously hypertensive rats.[3]

Reference:
[1]. Strobaek, D., Hougaard, C., Johansen, T.H., et al. Inhibitory gating modulation of small conductance Ca2+-activated K+ channels by the synthetic compound (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) reduces afterhyperpolarizing current in hippocampal CA1 neurons. Mol. Pharmacol. 70(5), 1771-1782 (2006).
[2]. Liu, B.-B., Peng, Y.-B., Zhang, W.-J., et al. NS8593 inhibits Ca2+ permeant channels reversing mouse airway smooth muscle contraction. Life Sci. 238:116953, (2019).
[3]. Diness, J.G., Skibsbye, L., Jespersen, T., et al. Effects on atrial fibrillation in aged hypertensive rats by Ca2+-activated K+ channel inhibition. Hypertension 57(6), 1129-1135 (2011).