Niflumic acid (Nifluril) is a Ca2+-activated Cl- channel blocker and an analgesic and anti-inflammatory agent used in the therapy of rheumatoid arthritis.

Niflumic acid suppresses calcium-activated currents on the basolateral membrane of rat pancreatic exocrine cells with an IC50 of 50 μM. It dose-dependently and reversibly activates the calcium-activated potassium (KCa) channels. Niflumic acid induces a spontaneous transient concentration-dependent inhibition of inward currents (STIC, calcium-activated chloride currents) amplitude. It inhibits calcium-activated chloride channels with a Ki of 17 mM. Additionally, Niflumic acid suppresses ICl(Ca) under the permeabilizing effect of Ca2+ on oocytes through Ca2+ ionophore A23187, suggesting the inhibition of ICl(Ca) results from direct interaction with Cl- channels, not by disruption of Ca2+ entry through voltage-dependent Ca2+ channels. Niflumic acid attenuates norepinephrine and caffeine-induced inward currents (IO(Ca)) with an IC50 of 6.6 μM, which is less effective than that on spontaneous currents. It exhibits a voltage-dependent inhibition of the amplitude of spontaneous transient currents (STIC), with IC50 values of 1.1 μM at +50 mV and 2.3 μM at -50 mV. Furthermore, Niflumic acid reduces airway hyperresponsiveness and eosinophilic infiltration, as well as inhibits IL-13 induced goblet cell hyperplasia. Following the IL-13 challenge, Niflumic acid hampers the overexpression of the MUC5AC gene (a marker of goblet cell proliferation) and levels of chemokines in bronchoalveolar lavage fluid. It also represses the activation of JAK/STAT6, AK2, and the expression of chemokines in epithelial cells.