ICA-27243

ICA-27243 is a selective, potent and orally active KCNQ2/Q3 potassium channel opener with an EC₅₀ of 0.38 μM. ICA-27243 is less effective at activating KCNQ4 and KCNQ3/Q5. ICA-27243 has antiepileptic and anticonvulsant effects^[1][2]. IC50 & Target: EC50: 0.38 μM (KCNQ2/Q3 potassium channel)^[2] In Vitro: In SH-SY5Y human neuroblastoma cells, ICA-27243 produces membrane potential hyperpolarization that could be prevented by coadministration with the M-current inhibitors XE-991 and Linopirdine. ICA-27243 enhances both ⁸⁶Rb⁺ efflux (EC₅₀ = 0.2 μM) and whole-cell currents in Chinese hamster ovary cells stably expressing heteromultimeric KCNQ2/Q3 channels (EC₅₀ = 0.4 μM). Activation of KCNQ2/Q3 channels is associated with a hyperpolarizing shift of the voltage dependence of channel activation (V_1/2 shift of -19 mV at 10 μM)^[1]. In Vivo: ICA-27243 (1-100 mg/kg; oral administration; male CD-1 mice) has anticonvulsant activity (ED₅₀ of 8.4 mg/kg) in the mouse maximal electroshock epilepsy model^[1].