In vitro activity: Niflumic acid inhibits Ca2+-activated Cl- channels with inhibition constant of 17 mM. Niflumic acid also inhibits ICl(Ca) elicited by bath application of Ca2+ to oocytes permeabilized using the Ca2+ ionophore A23187, demonstrating that the inhibition of ICl(Ca) is due to a direct interaction with the Cl- channel, rather than by interference with Ca2+ entry through voltage-dependent Ca2+ channels. Niflumic acid blocks Ca2+-activated non-selective cation channels in inside-out patches from the basolateral membrane of rat exocrine pancreatic cells with IC50 of 50 μM. Niflumic acid dose-dependently and reversibly activates large conductance calcium-activated K+ (KCa) channels. Niflumic acid produces a concentration-dependent inhibition of spontaneous transient inward current (STIC, calcium-activated chloride current) amplitude. Niflumic acid inhibits noradrenaline- and caffeine-evoked IO(Ca) with an ICM50 of 6.6 μM, i.e.is less potent against evoked currents compared to spontaneous currents. Niflumic acid voltage-dependently inhibits spontaneous transient inward current (STIC) amplitude with IC50 of 2.3 μM and 1.1 μM at -50 and +50 mV respectively. Niflumic acid inhibits not only IL-13-induced goblet cell hyperplasia but also airway hyperresponsiveness and eosinophilic infiltration. Niflumic suppresses the eotaxin levels in bronchoalveolar lavage fluids and overexpression of the MUC5AC gene, a marker of goblet cell hyperplasia, in the lung after IL-13 instillation. Niflumic acid suppresses JAK2 activation, STAT6 activation, and eotaxin expression in epithelial cells.

Mol Pharmacol. 1990 May;37(5):720-4; FEBS Lett. 1990 Jul 30;268(1):79-82.